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Toxics
Volume 11
Issue 4
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Toxics, Volume 11, Issue 4 (April 2023) – 106 articles

Cover Story (view full-size image): Contaminants of emerging concern, such as different substances of anti-seizure medication (ASM), are increasingly being detected in surface waters in Germany with unknown consequences on the health of non-target aquatic wildlife. Eurasian otters are top predators and thus susceptible to the bioaccumulation of pollutants. Potential contamination with ASM was investigated in otter brain samples by using HPLC and MS. Histologically, brain sections were analyzed for the presence of potential associated neuropathology. The studied groups consisted of 20 deceased wild otters and 5 individuals in human care. None of the targeted ASMs were detected and no obvious pathology was observed histologically, whereas their presence in the otter samples and related adverse effects could not be excluded. View this paper
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13 pages, 5202 KiB  
Article
Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines
by Won-Young Lee, Ran Lee and Hyun-Jung Park
Toxics 2023, 11(4), 397; https://doi.org/10.3390/toxics11040397 - 21 Apr 2023
Cited by 5 | Viewed by 2079
Abstract
Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups [...] Read more.
Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups in pesticides, but the mechanisms of TEB toxicity in bovine mammary gland epithelial cells (MAC-T cells) have not yet been studied. Damage to the mammary glands of dairy cows directly affects milk production. This study investigated the toxicological effects of TEB on MAC-T cells. We found that TEB decreases both cell viability and proliferation and activates apoptotic cell death via the upregulation of pro-apoptotic proteins, such as cleaved caspases 3 and 8 and BAX. TEB also induced endoplasmic reticulum (ER) stress via the upregulation of Bip/GRP78; PDI; ATF4; CHOP; and ERO1-Lα. We found that TEB induced mitochondria-mediated apoptotic MAC-T cell death by activating ER stress. This cell damage eventually led to a dramatic reduction in the expression levels of the milk-protein-synthesis-related genes LGB; LALA; CSN1S1; CSN1S2; and CSNK in MAC-T cells. Our data suggest that the exposure of dairy cows to TEB may negatively affect milk production by damaging the mammary glands. Full article
(This article belongs to the Section Agrochemicals and Food Toxicology)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Effects of TEB on viability, proliferation, and apoptosis of MAC-T cells. (<b>A</b>) MAC-T cell viability assessed by MTT assay. DMSO, cells treated with TEB (0–300 μM). (<b>B</b>) Morphological images of the cells observed under a microscope after 24 h treatment. Cells were treated with 0–200 μM of TEB in culture. Scaler bar = 20 μM. (<b>C</b>) The apoptotic cell death of MAC-T cells by TEB exposure was analyzed by flow cytometry at different concentrations (0–200 μM). Apoptotic cell death was determined by Annexin V-FITC/PI staining. (<b>D</b>) The graph shows the apoptosis rate, all data are presented as the mean ± SD of three independent experiments, and significance levels between control and treated are shown as asterisks (n = 4, ** <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 2
<p>The effects of TEB on MAC-T cell proliferation and pro-apoptotic protein expression. (<b>A</b>) Immunofluorescence analysis of Ki-67 in MAC-T cells after culture with 0–200 μm TEB. Scale bar = 50 μm. (<b>B</b>) Quantification of Ki-67-positive cells (Green) with respect to total cells (Blue) (%). Data are presented as mean ± SD (n = 4, ** <span class="html-italic">p</span> &lt; 0.001). (<b>C</b>) MAC-T cells were treated with the 0–200 μM TEB for 24 h, and then total protein was prepared and analyzed by immunoblotting. The protein expression levels of cleaved caspases 3 and 8, BAX, and β-actin in each experimental group. (<b>D</b>) The graph shows the densitometry analysis of protein bands normalized to β-actin. Data are presented as the mean ± SD (n = 4, * <span class="html-italic">p</span> &lt; 0.01, ** <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 3
<p>TEB induced loss of mitochondrial membrane potential in MAC-T cells. (<b>A</b>) Mitochondrial membrane potential in TEB-treated MAC-T cells was assessed using JC-1 staining. Red color indicates the accumulation of JC-1 aggregates, which indicates a normal mitochondrial membrane. Green color indicates JC-1 monomer with membrane depolarization. (<b>B</b>) Flow cytometry plots for MAC-T cells stained with JC-1 with TEB treatment (0–200 μM). (<b>C</b>) Relative ratios of green fluorescence (JC-1 monomer) represented as mitochondrial membrane potential (<span class="html-italic">∆Ψm</span>). Values represent the mean ± SD of three independent experiments (n = 3, ** <span class="html-italic">p</span> &lt; 0.001 compared to the controls).</p> Full article ">Figure 4
<p>The expression of ER-stress-related genes and proteins in TEB-treated MAC-T cells. (<b>A</b>) mRNA expression levels of CHOP, Bip/Grp78, and ATF4 in MAC-T cells by qPCR after 24 h of TEB treatment. (<b>B</b>) Immunoblots for detecting Bip/Grp78, ERO1-Lα, PDI, and β-actin in response to the exposure to different concentrations of TEB. (<b>C</b>) The graphs present the results of densitometric analysis. Each protein band was normalized using β-actin. Data represent the mean ± SD of three independent experiments (n = 3, * <span class="html-italic">p</span> &lt; 0.05, and ** <span class="html-italic">p</span> &lt; 0.001 compared to the controls).</p> Full article ">Figure 5
<p>The expression of milk-protein-synthesis-related genes in TEB-treated MAC-T cells. (<b>A</b>) mRNA expression levels of LGB, LALA, CSN1S1, CSN1S2, and CSNK, and (<b>B</b>) the gene expression levels of inflammatory genes TGFB3, CEBPD, and IL-6 in TEB-exposed MAC-T cells by qPCR. The graph represents the mean ± SD of three independent experiments (n = 4 * <span class="html-italic">p</span> &lt; 0.05, and ** <span class="html-italic">p</span> &lt; 0.001 compared to the controls).</p> Full article ">
17 pages, 2396 KiB  
Article
Risk Evaluation of Pollutants Emission from Coal and Coal Waste Combustion Plants and Environmental Impact of Fly Ash Landfilling
by Jovana Z. Buha Marković, Ana D. Marinković, Jasmina Z. Savić, Milica R. Mladenović, Milić D. Erić, Zoran J. Marković and Mirjana Đ. Ristić
Toxics 2023, 11(4), 396; https://doi.org/10.3390/toxics11040396 - 21 Apr 2023
Cited by 5 | Viewed by 2035
Abstract
Emission factors (EFs) of gaseous pollutants, particulate matter, certain harmful trace elements, and polycyclic aromatic hydrocarbons (PAHs) from three thermal power plants (TPPs) and semi-industrial fluidized bed boiler (FBB) were compared. EFs of particulate matter, trace elements (except Cd and Pb), benzo[a]pyrene, and [...] Read more.
Emission factors (EFs) of gaseous pollutants, particulate matter, certain harmful trace elements, and polycyclic aromatic hydrocarbons (PAHs) from three thermal power plants (TPPs) and semi-industrial fluidized bed boiler (FBB) were compared. EFs of particulate matter, trace elements (except Cd and Pb), benzo[a]pyrene, and benzo[b]fluoranthene exceed the upper limits specified in the EMEP inventory guidebook for all combustion facilities. The comparison of trace elements and PAHs content in fly ashes (FAs) from lignite and coal waste combustion in TPPs and FBB, respectively, as well as the potential environmental impact of FAs disposal, was performed by employing a set of ecological indicators such as crustal enrichment factor, risk assessment code, risk indices for trace elements, and benzo[a]pyrene equivalent concentration for PAHs. Sequential analysis shows that the trace elements portion is the lowest for water-soluble and exchangeable fractions. The highest enrichment levels in FAs are noticed for As and Hg. Based on toxic trace elements content, FAs from TPPs represent a very high ecological risk, whereas fly ash from FBB poses a moderate ecological risk but has the highest benzo[a]pyrene equivalent concentration, indicating its increased carcinogenic potential. Lead isotope ratios for Serbian coals and FAs can contribute to a lead pollution global database. Full article
(This article belongs to the Section Air Pollution and Health)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>NOx, CO, SO<sub>2</sub>, and total PM concentrations (all in mg/Nm<sup>3</sup>) in flue gases from TPP Kolubara A, TPP Kostolac B, TPP Nikola Tesla A, and FBB.</p> Full article ">Figure 2
<p>Overall trace element concentrations in F1-F6 fractions of fly ashes (TPPKb, TPPKs, TPPNT, and CFB).</p> Full article ">Figure 3
<p>Distribution of investigated trace elements in fly ashes: TPPKb (<b>a</b>), TPPKs (<b>b</b>), TPPNT (<b>c</b>), and CFB (<b>d</b>) among the water-soluble fraction (F1), the exchangeable fraction (F2), the carbonate bound fraction (F3), the metal oxide bound fraction (F4), the organic bound fraction (F5), and the residual fraction (F6).</p> Full article ">Figure 4
<p>(<b>a</b>) Portions for carcinogenic (C) and non-carcinogenic elements (NC) and average values in each fraction for all fly ashes (TPPKb, TPPKs, TPPNT, and CFB); (<b>b</b>) overall distribution of C and NC elements among six fractions.</p> Full article ">Figure 5
<p>(<b>a</b>) Three-dimensional diagram of Pb isotope ratios in fly ashes (TPPKb, TPPKs, TPPNT, and CFB) and correspondent coals (CKb, CKs, CNT, and CFBB); (<b>b</b>) range for <sup>206</sup>Pb/<sup>207</sup>Pb in different countries worldwide from west to east, i.e., USA: United States of America; S: Spain; UK: United Kingdom; B: Belgium; Sw: Switzerland; G: Germany; P: Poland; Se: Serbia; R: Russia; and Ch: China.</p> Full article ">Figure 6
<p>Crustal enrichment factor (<span class="html-italic">CEF<sub>n/Mn</sub></span>) for fly ashes (TPPKb, TPPKs, TPPNT, and CFB).</p> Full article ">Figure 7
<p>(<b>a</b>) Risk assessment code (RAC) and (<b>b</b>) risk index (RI) for fly ashes (TPPKb, TPPKs, TPPNT, and CFB).</p> Full article ">
15 pages, 1638 KiB  
Review
Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review
by Wenli Ding, Luxi Lin, Ke Yue, Yanfeng He, Bowen Xu, Aftab Shaukat and Shucheng Huang
Toxics 2023, 11(4), 395; https://doi.org/10.3390/toxics11040395 - 21 Apr 2023
Cited by 8 | Viewed by 2498
Abstract
Mycotoxin contamination has become one of the biggest hidden dangers of food safety, which seriously threatens human health. Understanding the mechanisms by which mycotoxins exert toxicity is key to detoxification. Ferroptosis is an adjustable cell death characterized by iron overload and lipid reactive [...] Read more.
Mycotoxin contamination has become one of the biggest hidden dangers of food safety, which seriously threatens human health. Understanding the mechanisms by which mycotoxins exert toxicity is key to detoxification. Ferroptosis is an adjustable cell death characterized by iron overload and lipid reactive oxygen species (ROS) accumulation and glutathione (GSH) depletion. More and more studies have shown that ferroptosis is involved in organ damage from mycotoxins exposure, and natural antioxidants can alleviate mycotoxicosis as well as effectively regulate ferroptosis. In recent years, research on the treatment of diseases by Chinese herbal medicine through ferroptosis has attracted more attention. This article reviews the mechanism of ferroptosis, discusses the role of ferroptosis in mycotoxicosis, and summarizes the current status of the regulation of various mycotoxicosis through ferroptosis by Chinese herbal interventions, providing a potential strategy for better involvement of Chinese herbal medicine in the treatment of mycotoxicosis in the future. Full article
(This article belongs to the Special Issue The Toxic Effects of Mycotoxins and Underlying Molecular Mechanisms)
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Figure 1
<p>Regulation of the ferroptosis pathway. In the iron cycle, excessive amounts of transferrin (TRF/TF) after binding to trivalent iron (Fe<sup>3+</sup>) may lead to iron overload, catalytic peroxidation, and accumulation of excessive intracellular ROS, resulting in DNA and mitochondrial DNA (mtDNA) damage. Lipid peroxidation (LPO) is the main cause of ferroptosis. LPO attacks PUFAs and expands the oxidation reaction under the action of lipoxygenases (LOXs), causing damage. GPX4 can catalyze the conversion of GSH into GSSG and reduce the intracellular toxic lipid peroxides or free H<sub>2</sub>O<sub>2</sub> into water. The consumption and activity reduction of GSH and GPX4 in the ferroptosis mechanism led to the decrease in ROS accumulation and LPO scavenging ability, which leads to ferroptosis.</p> Full article ">Figure 2
<p>Mycotoxin regulation ferroptosis diagram. The livestock and poultry are fed with feed contaminated by mycotoxins such as aflatoxin, zearalenone, T-2 toxin, and patulin, which promotes the production of ROS, down-regulates the expression levels of ferroptosis-related factors such as SLC7A11, Nrf2, SLC7A11, and GPX4, induces the damage of the biomacromolecular structure and oxidative stress, mitochondrial dysfunction, and leads to ferroptosis.</p> Full article ">Figure 3
<p>The picture shows the potential mechanisms of lycopene, curcumin, and algal polysaccharides in the treatment of aflatoxin B1. Lycopene mainly reduces aflatoxin damage by affecting the liver and kidneys. Natural polyphenol curcumin can effectively reduce afb1-induced BFH12 toxicity and reduce cell mortality. Algal polysaccharides can mitigate afb1-induced bursal damage in broiler chickens by regulating p38MAPK-Nrf2/HO-1 and mitochondrial apoptosis signaling pathways. AFB1, aflatoxin B1; OS, Oxidative stress; BFH12, Bovine Fetal Hepatocyte 12.</p> Full article ">
25 pages, 14169 KiB  
Article
Potential of Coupling Metaheuristics-Optimized-XGBoost and SHAP in Revealing PAHs Environmental Fate
by Gordana Jovanovic, Mirjana Perisic, Nebojsa Bacanin, Miodrag Zivkovic, Svetlana Stanisic, Ivana Strumberger, Filip Alimpic and Andreja Stojic
Toxics 2023, 11(4), 394; https://doi.org/10.3390/toxics11040394 - 21 Apr 2023
Cited by 9 | Viewed by 2586
Abstract
Polycyclic aromatic hydrocarbons (PAHs) refer to a group of several hundred compounds, among which 16 are identified as priority pollutants, due to their adverse health effects, frequency of occurrence, and potential for human exposure. This study is focused on benzo(a)pyrene, being considered an [...] Read more.
Polycyclic aromatic hydrocarbons (PAHs) refer to a group of several hundred compounds, among which 16 are identified as priority pollutants, due to their adverse health effects, frequency of occurrence, and potential for human exposure. This study is focused on benzo(a)pyrene, being considered an indicator of exposure to a PAH carcinogenic mixture. For this purpose, we have applied the XGBoost model to a two-year database of pollutant concentrations and meteorological parameters, with the aim to identify the factors which were mostly associated with the observed benzo(a)pyrene concentrations and to describe types of environments that supported the interactions between benzo(a)pyrene and other polluting species. The pollutant data were collected at the energy industry center in Serbia, in the vicinity of coal mining areas and power stations, where the observed benzo(a)pyrene maximum concentration for a study period reached 43.7 ngm−3. The metaheuristics algorithm has been used to optimize the XGBoost hyperparameters, and the results have been compared to the results of XGBoost models tuned by eight other cutting-edge metaheuristics algorithms. The best-produced model was later on interpreted by applying Shapley Additive exPlanations (SHAP). As indicated by mean absolute SHAP values, the temperature at the surface, arsenic, PM10, and total nitrogen oxide (NOx) concentrations appear to be the major factors affecting benzo(a)pyrene concentrations and its environmental fate. Full article
(This article belongs to the Special Issue Environmental Monitoring and Analysis of Persistent Organic Pollutants)
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<p>The Benzo(a)pyrene feature dataset split.</p> Full article ">Figure 2
<p>Visualized XGBoost results for all nine metaheuristics in terms of the convergence, box plot, violin diagrams, and swarm diversity plots for the fitness function (MSE).</p> Full article ">Figure 3
<p>Visualized XGBoost results for all nine metaheuristics in terms of the convergence, box plot, violin diagrams, and swarm diversity plots for the <math display="inline"><semantics> <msup> <mi>R</mi> <mn>2</mn> </msup> </semantics></math> indicator.</p> Full article ">Figure 4
<p>KDE diagrams for MSE (<b>left</b>) and <math display="inline"><semantics> <msup> <mi>R</mi> <mn>2</mn> </msup> </semantics></math> indicator (<b>right</b>).</p> Full article ">Figure 5
<p>Join plots with histograms of two best methods: HSA-SCA (<b>left</b>) and FA (<b>right</b>).</p> Full article ">Figure 6
<p>Best-predicted outcomes by the best produced models of HSA-SCA, FA, SCA and ChOA algorithms.</p> Full article ">Figure 6 Cont.
<p>Best-predicted outcomes by the best produced models of HSA-SCA, FA, SCA and ChOA algorithms.</p> Full article ">Figure 7
<p>Temperature at surface impact on benzo(a)pyrene.</p> Full article ">Figure 8
<p>Arsenic impact on benzo(a)pyrene.</p> Full article ">Figure 9
<p>Particulate matter impact on benzo(a)pyrene.</p> Full article ">Figure 10
<p>Nitrogen oxides impact on benzo(a)pyrene.</p> Full article ">
17 pages, 3122 KiB  
Review
Nrf2: A Main Responsive Element of the Toxicity Effect Caused by Trichothecene (T-2) Mycotoxin
by Youshuang Wang, Yu Liu, Tingyu Huang, Yunhe Chen, Wenxi Song, Fengjuan Chen, Yibao Jiang, Cong Zhang and Xu Yang
Toxics 2023, 11(4), 393; https://doi.org/10.3390/toxics11040393 - 21 Apr 2023
Cited by 5 | Viewed by 1854
Abstract
T-2 toxin, the most toxic type A trichothecene mycotoxin, is produced by Fusarium, and is widely found in contaminated feed and stored grains. T-2 toxin is physicochemically stable and is challenging to eradicate from contaminated feed and cereal, resulting in food contamination that [...] Read more.
T-2 toxin, the most toxic type A trichothecene mycotoxin, is produced by Fusarium, and is widely found in contaminated feed and stored grains. T-2 toxin is physicochemically stable and is challenging to eradicate from contaminated feed and cereal, resulting in food contamination that is inescapable and poses a major hazard to both human and animal health, according to the World Health Organization. Oxidative stress is the upstream cause of all pathogenic variables, and is the primary mechanism through which T-2 toxin causes poisoning. Nuclear factor E2-related factor 2 (Nrf2) also plays a crucial part in oxidative stress, iron metabolism and mitochondrial homeostasis. The major ideas and emerging trends in future study are comprehensively discussed in this review, along with research progress and the molecular mechanism of Nrf2’s involvement in the toxicity impact brought on by T-2 toxin. This paper could provide a theoretical foundation for elucidating how Nrf2 reduces oxidative damage caused by T-2 toxin, and a theoretical reference for exploring target drugs to alleviate T-2 toxin toxicity with Nrf2 molecules. Full article
(This article belongs to the Special Issue The Toxic Effects of Mycotoxins and Underlying Molecular Mechanisms)
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<p>Mechanism of the toxic effects of T-2 toxin.</p> Full article ">Figure 2
<p>Schematic diagram of the structure of Nrf2.</p> Full article ">Figure 3
<p>Mechanism of nephrotoxicity induced by T-2 toxin. T-2 toxin causes T-2 toxin leads to increased ROS and MDA contents and decreased expression of GSH, SOD, CAT, Nrf2, NQO1, HO-1, GCLC and GCLM, which leads to kidney damage.</p> Full article ">Figure 4
<p>Mechanism of hepatotoxicity induced by T-2 toxin. T-2 toxin leads to increased ROS and MDA contents and decreased expression of GSH, SOD, CAT and Nrf2, which leads to liver damage.</p> Full article ">Figure 5
<p>Mechanism of immunotoxicity induced by T-2 toxin.</p> Full article ">Figure 6
<p>Mechanism of neurotoxicity induced by T-2 toxin. T-2 toxins cause oxidative stress. Oxidative stress leads to mitochondrial damage (decreased MMP and ATP content, increased mitochondrial permeability, ROS production and increased cytochrome exudation), and mitochondrial damage leads to apoptosis (increased expression of caspase-3, caspase-9, BAX and P53, decreased expression of Bcl-2), which results in neurotoxicity. Increased expression of BAX and P53 exacerbates mitochondrial damage, and ROS produced by mitochondrial damage further increases oxidative stress. Oxidative stress leads to decreased Nrf2 expression, which in turn exacerbates oxidative stress. Oxidative stress leads to increased expression of HMGB1, which in turn leads to decreased expression of Nrf2 and increased expression of inflammatory factors (TNF-α, IL-6, IL-8 and IL-1β), and increased expression of inflammatory factors promotes cell apoptosis. Oxidative stress leads to increased expression of inflammatory factors. The relationship between Nrf2 and inflammation is unclear.</p> Full article ">Figure 7
<p>Mechanism of endocrine toxicity induced by T-2 toxin. Blue, yellow, gray, and white arrows, arrows up indicate increased expression and arrows down indicate decreased expression.</p> Full article ">Figure 8
<p>A current line of research on Nrf2 in T-2 toxin toxicity. T-2 toxin causes oxidative stress which affects Nrf2 expression. Nrf2 can increase anti-oxidative stress indicators, reduce apoptosis indicators, increase mitochondrial biogenesis indicators, affect autophagy indicators and affect inflammatory indicators.</p> Full article ">
20 pages, 2608 KiB  
Review
The Skin Sensitisation of Cosmetic Ingredients: Review of Actual Regulatory Status
by Iwona Bialas, Sandra Zelent-Kraciuk and Kamil Jurowski
Toxics 2023, 11(4), 392; https://doi.org/10.3390/toxics11040392 - 21 Apr 2023
Cited by 8 | Viewed by 4817
Abstract
All cosmetics products must be safe under foreseeable conditions of use. Allergenic responses are one of the most frequent adverse reactions noted for cosmetics. Thus, the EU cosmetics legislation requires skin sensitisation assessment for all cosmetics ingredients, including the regulated ones (for which [...] Read more.
All cosmetics products must be safe under foreseeable conditions of use. Allergenic responses are one of the most frequent adverse reactions noted for cosmetics. Thus, the EU cosmetics legislation requires skin sensitisation assessment for all cosmetics ingredients, including the regulated ones (for which the full toxicological dossier needs to be analysed by the Scientific Committee on Consumer Safety (SCCS)) and those (perceived as less toxic) which are assessed by industrial safety assessors. Regardless of who performs the risk assessment, it should be carried out using scientifically and regulatory body-accepted methods. In the EU, reference methods for chemical toxicity testing are defined in the relevant Annexes (VII–X) of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation. Recommendations for Skin Sensitization (Skin Sens) testing are provided in Annex VII, and this particular endpoint information is required for all EU-registered chemicals. Historically, in vivo animal and human methods have been used. Both raise ethical doubts, and some of them cause practical problems in the objective analysis of skin sensitising potency. Previous decades of huge effort have resulted in the regulatory acceptance of the alternative Skin Sens IATA (Integrated Approaches to Testing and Assessment) and NGRA (Next Generation Risk Assessment). Regardless of the testing issues, a serious sociological problem are observed within the market: the consumer assumes the presence of strong sensitisers in cosmetics formulations and insufficient risk management tools used by the industry. The present review aims to provide an overview of methods for assessing skin sensitisation. Additionally, it aims to answer the following question: what are the most potent skin sensitisers used in cosmetics? The answer considers the mechanistic background along with the actual regulatory status of ingredients and practical examples of responsible industry solutions in the area of risk management. Full article
(This article belongs to the Special Issue Human Health Risk Assessment, Environment Pollutants and Safety of Plant Materials, Herbal Medicinal Products and Diet Supplements)
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<p>The AOP concept with the main KE and the actual status of validated and scientifically accepted testing methods for skin sensitisation. Created with BioRender.com, accessed on 27 May 2023.</p> Full article ">
18 pages, 5282 KiB  
Article
Protective Effects of a Red Grape Juice Extract against Bisphenol A-Induced Toxicity in Human Umbilical Vein Endothelial Cells
by Caterina Russo, Alessandro Maugeri, Ambrogina Albergamo, Giacomo Dugo, Michele Navarra and Santa Cirmi
Toxics 2023, 11(4), 391; https://doi.org/10.3390/toxics11040391 - 21 Apr 2023
Cited by 4 | Viewed by 1850
Abstract
Human exposure to bisphenol A (BPA) occurs through the ingestion of contaminated food and water, thus leading to endothelial dysfunction, the first signal of atherosclerosis. Vitis vinifera L. (grape) juice is well known for its health-promoting properties, due to its numerous bioactive compounds [...] Read more.
Human exposure to bisphenol A (BPA) occurs through the ingestion of contaminated food and water, thus leading to endothelial dysfunction, the first signal of atherosclerosis. Vitis vinifera L. (grape) juice is well known for its health-promoting properties, due to its numerous bioactive compounds among which are polyphenols. The aim of this study was to evaluate the protective effect of a red grape juice extract (RGJe) against the endothelial damage induced by BPA in human umbilical vein endothelial cells (HUVECs) as an in vitro model of endothelial dysfunction. Our results showed that RGJe treatment counteracted BPA-induced cell death and apoptosis in HUVECs, blocking caspase 3 and modulating p53, Bax, and Bcl-2. Moreover, RGJe demonstrated antioxidant properties in abiotic tests and in vitro, where it reduced BPA-induced reactive oxygen species as well as restored mitochondrial membrane potential, DNA integrity, and nitric oxide levels. Furthermore, RGJe reduced the increase of chemokines (IL-8, IL-1β, and MCP-1) and adhesion molecules (VCAM-1, ICAM-1, and E-selectin), caused by BPA exposure, involved in the primary phase of atheromatous plaque formation. Overall, our results suggest that RGJe prevents BPA-induced vascular damage modulating specific intracellular mechanisms, along with protecting cells, owing to its antioxidant capability. Full article
(This article belongs to the Special Issue Toxicological Effects of Endocrine-Disrupting Chemicals on Human Health)
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<p>Protective effect of RGJe against BPA-induced cytotoxicity in HUVECs. Cell viability was evaluated by MTT test (<bold>A</bold>) and cell proliferation via BrdU incorporation test (<bold>B</bold>). Results of both assays are expressed as percentages ± SEM of the absorbance value detected in treated cells compared to untreated ones (control, CTRL). Three independent experiments in eight replicates were performed (n = 24). ** <italic>p</italic> &lt; 0.01 and **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °°° <italic>p</italic> &lt; 0.001, and °°°° <italic>p</italic> &lt; 0.0001 vs. BPA 300 µM.</p> Full article ">Figure 2
<p>RGJe reduced both ROS generation and fall of ∆Ψm induced by BPA in HUVECs. Cytofluorimetric evaluation of intracellular ROS (<bold>A</bold>) and mitochondrial membrane potential (<bold>B</bold>) was carried out employing DCFH-DA and R123 fluorescent probes, respectively. Representative plots of three independent experiments performed in triplicate (n = 9) are shown. For ROS detection (<bold>A</bold>) the histograms show the percentage ± SEM of healthy cells (DCF−, M1) and cells with increased intracellular ROS (DCF<sup>+</sup>, M2) of three separate experiments in triplicate (n = 9). For ∆Ψm evaluation the histograms represent the percentage ± SEM of healthy cells (R123<sup>+</sup>, M2) and the cells with impaired mitochondrial membrane potential (R123−, M1) of three separate experiments in triplicate (n = 9).</p> Full article ">Figure 3
<p>Protective effect of RGJe against the DNA oxidative damage induced by BPA in HUVECs. Levels of 8-oxo-dG were measured by flow cytometry, detecting the emission signals of fluorochrome FITC-labeled avidin. Representative plots of three different experimental sessions performed in triplicate (n = 9) are displayed (<bold>A</bold>). The histogram reports the percentage ± SEM of healthy (non-fluorescent, M1) and damaged (fluorescent, M2) cells (<bold>B</bold>), from three independent experiments performed in triplicate (n = 9).</p> Full article ">Figure 4
<p>Effect of the pre-treatment with RGJe on antioxidant defense systems reduced by BPA in HUVECs. The activity of SOD (<bold>A</bold>) and CAT (<bold>B</bold>), as well as GSH levels (<bold>C</bold>) are reported. Data are expressed as the mean ± SEM of three separate experiments performed in triplicate (n = 9). **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °° <italic>p</italic> &lt; 0.01, °°° <italic>p</italic> &lt; 0.001 vs. BPA 300 µM.</p> Full article ">Figure 5
<p>Effect of RGJe on reduction of NO release induced by BPA in HUVECs. The NO levels were determined by a colorimetric assay. Data are expressed as the percentage value of NO detected in treated cells compared to untreated ones and are shown as mean ± SEM from three independent experiments performed in triplicate (n = 9). **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °°° <italic>p</italic> &lt; 0.001, and °°°° <italic>p</italic> &lt; 0.0001 vs. BPA 300 µM.</p> Full article ">Figure 6
<p>RGJe reduced the BPA-induced apoptotic cell death and modulated Casp3 enzymatic activity and apoptotic-related genes in HUVECs. Evaluation of apoptosis was performed cytofluorimetrically by the Annexin V-FITC/PI test (<bold>A</bold>). Representative Annexin V vs. PI dot plots are shown where necrotic (Annexin V−/PI+), late apoptosis (Annexin V+/PI+), viable (Annexin V−/PI−), and early apoptosis (Annexin V+/PI−) cells are in Q4, Q3, Q1, and Q2, respectively. The histograms report the percentage of cells for each quadrant, expressed as the mean ± SEM of three experiments in triplicate (n = 9) (<bold>B</bold>). The mRNA levels of apoptosis-related genes BAX, BCL-2, P53, and CASP3 were quantified via RT-PCR using the 2<sup>−ΔΔCT</sup> method. Data are expressed as n-fold change relative to the untreated cells, reporting the obtained values from three independent experiments performed in triplicate (n = 9) (<bold>C</bold>). Data of caspase 3 enzymatic activity are expressed as the percentage of the value detected in treated cells compared to the untreated ones and are displayed as the mean ± SEM of three experiments in triplicate (n = 9) (<bold>D</bold>). *** <italic>p</italic> &lt; 0.001 and **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °° <italic>p</italic> &lt; 0.01, °°° <italic>p</italic> &lt; 0.001, and °°°° <italic>p</italic> &lt; 0.0001 vs. BPA 300 µM.</p> Full article ">Figure 7
<p>Effect of RGJe on IL-8 and IL-1β cytokines and MCP-1 chemokine gene expression in BPA-treated HUVECs. The results from RT-PCR of IL-8 (<bold>A</bold>), IL-1β (<bold>B</bold>), and MCP-1 (<bold>C</bold>) are expressed as an n-fold change compared to untreated cells after normalization against β-actin as endogenous control. Data represent the mean ± SEM of three different sets of experiments performed in triplicate (n = 9). **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °° <italic>p</italic> &lt; 0.01, °°° <italic>p</italic> &lt; 0.001, and °°°° <italic>p</italic> &lt; 0.0001 vs. BPA 300 µM.</p> Full article ">Figure 8
<p>RGJe reduced the BPA-induced mRNA increase of VCAM-1, ICAM-1, and E-selectin adhesion molecules in HUVECs. The results from RT-PCR are expressed as an n-fold change compared to untreated cells, after normalization against β-actin as endogenous control. Data represent the mean ± SEM of three different sets of experiments performed in triplicate (n = 9). ** <italic>p</italic> &lt; 0.01, *** <italic>p</italic> &lt; 0.001, and **** <italic>p</italic> &lt; 0.0001 vs. CTRL; ° <italic>p</italic> &lt; 0.05, °° <italic>p</italic> &lt; 0.01, °°° <italic>p</italic> &lt; 0.001, and °°°° <italic>p</italic> &lt; 0.0001 vs. BPA 300 µM.</p> Full article ">Figure 9
<p>Heatmap of gene expression modulated by RGJe. The columns of the heatmap represent each treatment and the rows indicate the genes. Each cell is colored based on the amount of the gene found in that sample.</p> Full article ">
14 pages, 1726 KiB  
Article
Cadmium-Induced Tubular Dysfunction in Type 2 Diabetes: A Population-Based Cross-Sectional Study
by Soisungwan Satarug, Supabhorn Yimthiang, Phisit Pouyfung, Tanaporn Khamphaya and David A. Vesey
Toxics 2023, 11(4), 390; https://doi.org/10.3390/toxics11040390 - 21 Apr 2023
Cited by 1 | Viewed by 1914
Abstract
The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of β2-microglobulin (β [...] Read more.
The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of β2-microglobulin (β2M) above 300 µg/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics (n = 81) and non-diabetics (n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and β2M excretion rates (ECd and Eβ2M) to creatinine clearance (Ccr) as ECd/Ccr and Eβ2M/Ccr. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold (p < 0.001) and 3-fold (p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of ECd/Ccr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% (p < 0.001) and 15% (p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, Eβ2M/Ccr was associated with ECd/Ccr (β = 0.375, p = 0.001) and obesity (β = 0.273, p = 0.015). In the non-diabetic group, Eβ2M/Ccr was associated with age (β = 0.458, p < 0.001) and ECd/Ccr (β = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), Eβ2M/Ccr was higher in the diabetics than non-diabetics of similar ECd/Ccr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden. Full article
(This article belongs to the Special Issue 10th Anniversary of Toxics: Women's Special Issue Series)
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Figure 1

Figure 1
<p>Effects of diabetes and cadmium exposure on β<sub>2</sub>M excretion. Scatterplot (<b>a</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>] in all diabetic and all non-diabetic participants. Bar graph (<b>b</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] in all diabetic and non-diabetics grouped by ranges of log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>]. Scatterplot (<b>c</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>] in diabetics from Pakpoon and all non-diabetics. Bar graph (<b>d</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] in diabetics from Pakpoon and all non-diabetics grouped by ranges of log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>]. Coefficients of determination (R<sup>2</sup>) and <span class="html-italic">p</span>-values are provided for all scatterplots. Mean values were adjusted for age, BMI, and interactions. Units of E<sub>β2M</sub>/C<sub>cr</sub> and E<sub>Cd</sub>/C<sub>cr</sub> are ng/L of filtrate.</p> Full article ">Figure 2
<p>Excretion rates of β<sub>2</sub>M in relation to eGFR reduction. Scatterplot (<b>a</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to eGFR in all diabetics. Graph (<b>b</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] and the variability of each mean in diabetics grouped by ranges of eGFR. Scatterplot (<b>c</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to eGFR among non-diabetics. Graph (<b>d</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] and the variability of each mean in diabetics grouped by ranges of eGFR. Coefficients of determination (R<sup>2</sup>) and <span class="html-italic">p</span>-values are provided for all scatterplots. Mean values were adjusted for covariates and interactions. Unit of E<sub>β2M</sub>/C<sub>cr</sub> is µg/L of filtrate, and the unit of eGFR is mL/min/1.73 m<sup>2</sup>.</p> Full article ">Figure 2 Cont.
<p>Excretion rates of β<sub>2</sub>M in relation to eGFR reduction. Scatterplot (<b>a</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to eGFR in all diabetics. Graph (<b>b</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] and the variability of each mean in diabetics grouped by ranges of eGFR. Scatterplot (<b>c</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to eGFR among non-diabetics. Graph (<b>d</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] and the variability of each mean in diabetics grouped by ranges of eGFR. Coefficients of determination (R<sup>2</sup>) and <span class="html-italic">p</span>-values are provided for all scatterplots. Mean values were adjusted for covariates and interactions. Unit of E<sub>β2M</sub>/C<sub>cr</sub> is µg/L of filtrate, and the unit of eGFR is mL/min/1.73 m<sup>2</sup>.</p> Full article ">Figure 3
<p>Increments of β<sub>2</sub>M excretion as a function of kidney cadmium burden and GFR. Scatterplot (<b>a</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>] in diabetics grouped by eGFR levels &gt; 60 and ≤60 mL/min/1.73 m<sup>2</sup>. Bar graph (<b>b</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] in diabetics grouped by eGFR and ranges of E<sub>Cd</sub>/C<sub>cr</sub>. Scatterplot (<b>c</b>) relates log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] to log[(E<sub>Cd</sub>/C<sub>cr</sub>) × 10<sup>5</sup>] in non-diabetics grouped by eGFR levels &gt; 60 and ≤60 mL/min/1.73 m<sup>2</sup>. Graph (<b>d</b>) depicts mean log[(E<sub>β2M</sub>/C<sub>cr</sub>) × 10<sup>4</sup>] in non-diabetics grouped by eGFR and ranges of E<sub>Cd</sub>/C<sub>cr</sub>. Coefficients of determination (R<sup>2</sup>) and <span class="html-italic">p</span>-values are provided for all scatterplots. Mean values were adjusted for age and BMI differences, and interactions. Units of E<sub>β2M</sub>/C<sub>cr</sub> and E<sub>Cd</sub>/C<sub>cr</sub> are ng/L of filtrate, and the unit of eGFR is mL/min/1.73 m<sup>2</sup>.</p> Full article ">
12 pages, 1871 KiB  
Article
Exposure and Risk Assessment to Airborne dl-PCBs and Dioxins in the Population Living in the Neighborhood of a Cement Plant: A Pilot Study in the Valencian Region of Spain
by Pablo Ruiz, Iñaki Lacomba, Antonio López, Vicent Yusà and Clara Coscollà
Toxics 2023, 11(4), 389; https://doi.org/10.3390/toxics11040389 - 20 Apr 2023
Cited by 1 | Viewed by 1501
Abstract
Emissions from cement manufacturing facilities may increase health risks in nearby populations. For this reason, dioxin-like PCB (dl-PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) concentrations in PM10 samples were assessed in the vicinity of a cement manufacturing plant located in the [...] Read more.
Emissions from cement manufacturing facilities may increase health risks in nearby populations. For this reason, dioxin-like PCB (dl-PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) concentrations in PM10 samples were assessed in the vicinity of a cement manufacturing plant located in the Valencian Region (eastern Spain). The total concentrations of the sum of dl-PCBs, PCDDs, and PCDFs ranged between 1.85 and 42.53 fg TEQ/m3 at the assessed stations. The average daily inhalation dose (DID) for the sum in adults ranged from 8.93 · 10−4 to 3.75 · 10−3 pg WHO TEQ kg−1 b.w. d−1, and, for children, the DID ranged from 2.01 · 10−3 to 8.44 · 10−3 pg WHO TEQ kg−1 b.w. d−1. Risk assessment for adults and children was performed using both daily and chronic exposure. The hazard quotient (HQ) was calculated considering 0.025 pg WHO TEQ kg−1 b.w. d−1 to be the acceptable maximum permitted inhalation exposure. The HQ obtained was slightly higher than 1 for PCDD/Fs at one of the stations (Chiva), indicating a possible health risk for the population under study due to inhalation exposure. In the case of chronic exposure, cancer risk (>10−6) was observed for some samples in one of the assessed sampling sites (Chiva). Full article
(This article belongs to the Special Issue The Latest Advances in Air Pollution and Human Health)
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<p>Location of the evaluated stations (S1 and S2) and cement plant.</p> Full article ">Figure 2
<p>Dioxin and dl-PCB levels detected (fg TEQ/m<sup>3</sup>) at Chiva (<b>S1</b>) and Buñol (<b>S2</b>) stations.</p> Full article ">Figure 3
<p>Hazard quotient at Chiva and Buñol stations for adults and children.</p> Full article ">Figure 4
<p>Cancer risk at Chiva (<b>A</b>) and Buñol stations (<b>B</b>).</p> Full article ">Figure 4 Cont.
<p>Cancer risk at Chiva (<b>A</b>) and Buñol stations (<b>B</b>).</p> Full article ">
15 pages, 3993 KiB  
Article
Trans- and Multigenerational Effects of Isothiazolinone Biocide CMIT/MIT on Genotoxicity and Epigenotoxicity in Daphnia magna
by Jiwan Kim and Jinhee Choi
Toxics 2023, 11(4), 388; https://doi.org/10.3390/toxics11040388 - 20 Apr 2023
Cited by 6 | Viewed by 2720
Abstract
The mixture of 5-chloro-2-methylisothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one, CMIT/MIT, is an isothiazolinone biocide that is consistently detected in aquatic environments because of its broad-spectrum usage in industrial fields. Despite concerns about ecotoxicological risks and possible multigenerational exposure, toxicological information on CMIT/MIT is very limited to [...] Read more.
The mixture of 5-chloro-2-methylisothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one, CMIT/MIT, is an isothiazolinone biocide that is consistently detected in aquatic environments because of its broad-spectrum usage in industrial fields. Despite concerns about ecotoxicological risks and possible multigenerational exposure, toxicological information on CMIT/MIT is very limited to human health and within-generational toxicity. Furthermore, epigenetic markers altered by chemical exposure can be transmitted over generations, but the role of these changes in phenotypic responses and toxicity with respect to trans- and multigenerational effects is poorly understood. In this study, the toxicity of CMIT/MIT on Daphnia magna was evaluated by measuring various endpoints (mortality, reproduction, body size, swimming behavior, and proteomic expression), and its trans- and multigenerational effects were investigated over four consecutive generations. The genotoxicity and epigenotoxicity of CMIT/MIT were examined using a comet assay and global DNA methylation measurements. The results show deleterious effects on various endpoints and differences in response patterns according to different exposure histories. Parental effects were transgenerational or recovered after exposure termination, while multigenerational exposure led to acclimatory/defensive responses. Changes in DNA damage were closely associated with altered reproduction in daphnids, but their possible relationship with global DNA methylation was not found. Overall, this study provides ecotoxicological information on CMIT/MIT relative to multifaceted endpoints and aids in understanding multigenerational phenomena under CMIT/MIT exposure. It also emphasizes the consideration of exposure duration and multigenerational observations in evaluating ecotoxicity and the risk management of isothiazolinone biocides. Full article
(This article belongs to the Special Issue Epigenetic Changes in Organisms Stressed by Environmental Pollution)
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Full article ">Figure 1
<p>Experimental workflow for multigenerational studies: (<b>A</b>) Illustration of three different exposure designs (control, parental exposure, and multigenerational exposure) across four generations (P0: parental generation; F1: first filial generation; F2: second filial generation; F3: third filial generation). The third clutch of female daphnids was used for the next generation. (<b>B</b>) Detailed experimental schedules for the assessment of various endpoints within a single generation. Exposure was initiated with neonates on day 0 and ended on day 21.</p> Full article ">Figure 2
<p>Effects of CMIT/MIT on mortality and reproductive capacity in <span class="html-italic">D. magna</span>: (<b>A</b>) Survival rate of daphnid neonates exposed for 48 h to 20, 40, 80, 160, and 320 µg/L CMIT/MIT. Data are presented as means ± SE (n = 4). (<b>B</b>) Total offspring numbers of adult daphnids exposed for 21 days to 5, 10, 20, 40, and 80 µg/L CMIT/MIT. Data are presented as means ± SE (n = 10). Asterisks indicate the significant differences between the exposure and control groups: * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">Figure 3
<p>Reproductive capacity, growth, and swimming behavior of <span class="html-italic">D. magna</span> after exposure to EC20 CMIT/MIT (7 µg/L): (<b>A</b>) Number of offspring per clutch and total number of offspring produced by adult daphnids exposed to CMIT/MIT for 21 days. (<b>B</b>) Growth of daphnids was observed on days 0, 7, and 21 after exposure to CMIT/MIT. (<b>C</b>) The quantitative value of behavioral parameters (speed, locomotory rate, stop number, turning rate, and path length). (<b>D</b>) The representative pictures of two-dimensional pathway (four images were selected) in the control and exposure groups. Data are presented as means ± SE (n = 10), with the asterisks indicating significant differences between the exposure and control groups: ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">Figure 4
<p>Protein–protein interaction networks and functional enrichments of differentially expressed proteins (DEPs) in <span class="html-italic">D. magna</span> after exposure to EC<sub>20</sub> CMIT/MIT: KEGG pathways and GO molecular functions were enriched among (<b>A</b>) upregulated proteins and (<b>B</b>) downregulated proteins.</p> Full article ">Figure 5
<p>Phenotypic responses of daphnids to parental and multigenerational exposure to CMIT/MIT EC<sub>20</sub>. Data are normalized to the means of each control group and presented as normalized values ± SE (n = 10). Asterisks indicate significant differences between the exposure and control groups: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001. (<b>A</b>) Total number of neonates produced by adult daphnids. (<b>B</b>) First reproduction time of daphnids. (<b>C</b>) Body length of 7-day-old daphnid. (<b>D</b>) Representative images of the morphology and egg-holding rate (%) of daphnids under the two exposure scenarios. % indicates the percentage of organisms that had eggs or progenies in the brood chamber.</p> Full article ">Figure 6
<p>Genotoxic and epigenetic responses of daphnids to parental and multigenerational exposure to EC<sub>20</sub> CMIT/MIT: (<b>A</b>) Comparison of the measured DNA damage with the representative images of tail moment. (<b>B</b>) Comparison of % global DNA methylation. Asterisks indicate significant differences between the exposure and control groups: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001. Letters denote the homogeneity between groups (Bonferroni’s test).</p> Full article ">
16 pages, 5462 KiB  
Article
Parabens Increase Sulfamethoxazole-, Tetracycline- and Paraben-Resistant Bacteria and Reshape the Nitrogen/Sulfur Cycle-Associated Microbial Communities in Freshwater River Sediments
by Chu-Wen Yang and Wei-Chen Lee
Toxics 2023, 11(4), 387; https://doi.org/10.3390/toxics11040387 - 18 Apr 2023
Cited by 4 | Viewed by 1655
Abstract
Backgrounds Parabens are pollutants of emerging concern in aquatic environments. Extensive studies regarding the occurrences, fates and behavior of parabens in aquatic environments have been reported. However, little is known about the effects of parabens on microbial communities in freshwater river sediments. This [...] Read more.
Backgrounds Parabens are pollutants of emerging concern in aquatic environments. Extensive studies regarding the occurrences, fates and behavior of parabens in aquatic environments have been reported. However, little is known about the effects of parabens on microbial communities in freshwater river sediments. This study reveals the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on antimicrobial-resistant microbiomes, nitrogen/sulfur cycle-associated microbial communities and xenobiotic degrading microbial communities in freshwater river sediments. Methods The river water and sediments collected from the Wai-shuangh-si Stream in Taipei City, Taiwan were used to construct a model system in fish tanks to test the effects of parabens in laboratory. Results Tetracycline-, sulfamethoxazole- and paraben-resistant bacteria increased in all paraben treated river sediments. The order of the overall ability to produce an increment in sulfamethoxazole-, tetracycline- and paraben-resistant bacteria was MP > EP > PP > BP. The proportions of microbial communities associated with xenobiotic degradation also increased in all paraben-treated sediments. In contrast, penicillin-resistant bacteria in both the aerobic and anaerobic culture of paraben-treated sediments decreased drastically at the early stage of the experiments. The proportions of four microbial communities associated with the nitrogen cycle (anammox, nitrogen fixation, denitrification and dissimilatory nitrate reduction) and sulfur cycle (thiosulfate oxidation) largely increased after the 11th week in all paraben-treated sediments. Moreover, methanogens and methanotrophic bacteria increased in all paraben-treated sediments. In contrast, the nitrification, assimilatory sulfate reduction and sulfate-sulfur assimilation associated to microbial communities in the sediments were decreased by the parabens. The results of this study uncover the potential effects and consequences of parabens on microbial communities in a freshwater river environment. Full article
(This article belongs to the Section Emerging Contaminants)
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<p>Plate counts of sulfamethoxazole- (<b>A</b>–<b>H</b>) and tetracycline- (<b>I</b>–<b>P</b>) resistant microbes in paraben-treated river sediments. (<b>A</b>–<b>D</b>,<b>I</b>–<b>L</b>) aerobic culture. (<b>E</b>–<b>H</b>,<b>M</b>–<b>P</b>) anaerobic culture. <span class="html-italic">Y</span>-axis indicates colony forming unit per mL (CFU/mL). <span class="html-italic">X</span>-axis indicates weeks (0–18th week). Data from triplicate assays are presented as the mean ± SE. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 2
<p>Plate counts of paraben- (<b>A</b>–<b>H</b>) and penicillin- (<b>I</b>–<b>P</b>) resistant microbes in paraben-treated river sediments. (<b>A</b>–<b>D</b>,<b>I</b>–<b>L</b>) aerobic culture. (<b>E</b>–<b>H</b>,<b>M</b>–<b>P</b>) anaerobic culture. <span class="html-italic">Y</span>-axis indicates colony forming unit per mL (CFU/mL). <span class="html-italic">X</span>-axis indicates weeks (0–18th week). Data from triplicate assays are presented as the mean ± SE. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 3
<p>Chemical compositions of the river waters. (<b>A</b>) sulfide (S<sup>2−</sup>), (<b>B</b>) sulfate (SO<sub>4</sub><sup>2−</sup>), (<b>C</b>) chemical oxygen demand (COD), (<b>D</b>) pH, (<b>E</b>) nitrate (NO<sub>3</sub><sup>−</sup>), (<b>F</b>) nitrite (NO<sub>2</sub><sup>−</sup>), (<b>G</b>) ammonium (NH<sub>4</sub><sup>+</sup>), and (<b>H</b>) oxidation-reduction potential (ORP). <span class="html-italic">X</span>-axis indicates weeks (0–18th week). Data from triplicate assays are presented as the mean ± SE. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 4
<p>Identification of various common and known microbial genera from different paraben-treated river sediments. (<b>A</b>) Comparison (NMDS analysis) of microbiome compositions between different paraben-treated river sediments. (<b>B</b>) Venn diagram analysis and number of microbial genera increased in paraben treated river sediments. (<b>C</b>) Venn diagram analysis and number of microbial genera decreased in paraben treated river sediments. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben.</p> Full article ">Figure 5
<p>Proportion changes in the nitrogen cycle-associated microbial communities in the paraben-treated river sediments. (<b>A</b>) Anammox (anaerobic ammonium oxidation) (<b>B</b>) Nitrogen fixation (M00175: nitrogen =&gt; ammonia) (<b>C</b>) Denitrification (M00529: nitrate =&gt; nitrogen) (<b>D</b>) Dissimilatory nitrate reduction (M00530: nitrate =&gt; ammonia) (<b>E</b>) Nitrification (M00528: ammonia =&gt; nitrite) (<b>F</b>) Assimilatory nitrate reduction (M00531: nitrate =&gt; ammonia). “1st” indicates the meaning of the period between week 0 and week 8. “2nd” indicates the meaning of the period between week 8 and week 17. Red star indicates the <span class="html-italic">p</span> value of the Mann–Whitney U test &lt; 0.05 (compared with control (CT)). Prop: proportions of microbial genera. “M00xxx” indicates the meaning of the KEGG module ID number. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 6
<p>Proportion changes of S cycle-associated microbial communities in the paraben-treated river sediments. (<b>A</b>) Thiosulfate oxidation (M00595: thiosulfate =&gt; sulfate). (<b>B</b>) Assimilatory sulfate reduction (M00176: sulfate =&gt; H<sub>2</sub>S). (<b>C</b>) Sulfate-sulfur assimilation (M00616). (<b>D</b>) Dissimilatory sulfate reduction (M00596: sulfate =&gt; H<sub>2</sub>S). “1st” indicates the meaning of the period between week 0 and week 8. “2nd” indicates the meaning of the period between week 8 and week 17. Red star indicates the <span class="html-italic">p</span> value of the Mann–Whitney U test &lt; 0.05 (compared with control (CT)). Prop: proportions of microbial genera. “M00xxx” indicates the meaning of the KEGG module ID number. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 7
<p>Proportion changes of microbial communities in the paraben-treated river sediments. (<b>A</b>) Bacterial genera associated with xenobiotics degradation. (<b>B</b>) Microbial genera with potential pathogenic bacteria. “1st” indicates the meaning of the period between week 0 and week 8. “2nd” indicates the meaning of the period between week 8 and week 17. Red star indicates the <span class="html-italic">p</span> value of the Mann–Whitney U test &lt; 0.05 (compared with control (CT)). Prop: proportions of microbial genera. “M00xxx” indicates the meaning of the KEGG module ID number. MP: methylparaben, EP: ethylparaben, PP: propylparaben, BP: butylparaben, CT: control.</p> Full article ">Figure 8
<p>Effects of parabens on microbiomes in the freshwater river sediments revealed in this study. (<b>A</b>) Nitrogen cycle-associated microbial communities. (<b>B</b>) Sulfur cycle-associated microbial communities. Red arrows indicate increase of microbes. Green arrows indicate decrease of microbes. “M00xxx” indicates KEGG module ID number.</p> Full article ">
14 pages, 625 KiB  
Article
Effects of COVID-19 Disease on DNA Damage, Oxidative Stress and Immune Responses
by M. Mert Basaran, Merve Hazar, Mehtap Aydın, Gülsüm Uzuğ, İlkima Özdoğan, Emin Pala, Sevtap Aydın Dilsiz and Nursen Basaran
Toxics 2023, 11(4), 386; https://doi.org/10.3390/toxics11040386 - 18 Apr 2023
Cited by 9 | Viewed by 1884
Abstract
Coronavirus disease 2019 (COVID-19) has posed a great threat to public health and has caused concern due to its fatal consequences over the last few years. Most people with COVID-19 show mild-to-moderate symptoms and recover without the need for special treatment, while others [...] Read more.
Coronavirus disease 2019 (COVID-19) has posed a great threat to public health and has caused concern due to its fatal consequences over the last few years. Most people with COVID-19 show mild-to-moderate symptoms and recover without the need for special treatment, while others become seriously ill and need medical attention. Additionally, some serious outcomes, such as heart attacks and even stroke, have been later reported in patients who had recovered. There are limited studies on how SARS-CoV-2 infection affects some molecular pathways, including oxidative stress and DNA damage. In this study, we aimed to evaluate DNA damage, using the alkaline comet assay, and its relationship with oxidative stress and immune response parameters in COVID-19-positive patients. Our results show that DNA damage, oxidative stress parameters and cytokine levels significantly increased in SARS-CoV-2-positive patients when compared with healthy controls. The effects of SARS-CoV-2 infection on DNA damage, oxidative stress and immune responses may be crucial in the pathophysiology of the disease. It is suggested that the illumination of these pathways will contribute to the development of clinical treatments and to reduce adverse effects in the future. Full article
(This article belongs to the Special Issue Biological Risk Monitoring of Exposure to Chemical Pollutants and/or Physical Agents)
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<p>DNA damage in lymphocytes of the study groups using the alkaline comet assay. DNA damage was expressed as DNA tail intensity (% of DNA in the tail) in lymphocytes. The values are given as means ± standard error mean (min–max). * <span class="html-italic">p</span> &lt; 0.05, compared with healthy controls; # <span class="html-italic">p</span> &lt; 0.05, patients with severe symptoms compared with patients with mild symptoms.</p> Full article ">
19 pages, 7705 KiB  
Article
Concept Development and Field Testing of Wireless Outdoor Indicator System for Use in Monitoring Exposures at Work among Malaysian Traffic Police
by Putri Anis Syahira Mohamad Jamil, Nur Athirah Diyana Mohammad Yusof, Karmegam Karuppiah, Irniza Rasdi, Vivien How, Shamsul Bahri Mohd Tamrin, Muhammad Hasnolhadi Samsudin, Sivasankar Sambasivam and Nayef Shabbab Almutairi
Toxics 2023, 11(4), 385; https://doi.org/10.3390/toxics11040385 - 18 Apr 2023
Cited by 1 | Viewed by 1420
Abstract
Real-time exposure air monitoring is essential to protect the respiratory health of the Malaysian traffic police. However, the data from monitoring stations have been inadequate to provide accurate information about their exposure. This report describes the conceptual design of a wireless exposure indicator [...] Read more.
Real-time exposure air monitoring is essential to protect the respiratory health of the Malaysian traffic police. However, the data from monitoring stations have been inadequate to provide accurate information about their exposure. This report describes the conceptual design of a wireless exposure indicator system, and then evaluates the field performance of the system by collocation. The study tested the accuracy of particulate matter size 2.5 (PM2.5), carbon monoxide (CO), and nitrogen dioxide (NO2) by comparing the measurements from the prototype with the measurements from reference instruments. The field testing found that the data tested were significantly correlated with each other (PM2.5-rs = 0.207, p = 0.019; NO2-rs = 0.576, p = 0.02 and CO-rs = 0.545, p = 0.04). The prototype proved to be successful as it can compute and transmit real-time monitoring data on the level of exposure to harmful air. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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<p>Summary of the design process.</p> Full article ">Figure 2
<p>Criteria of the proposed system.</p> Full article ">Figure 3
<p>Stationary field-testing locations. The red star indicates the exact position where the prototype was deployed. (Source: Google Maps available at <a href="https://www.google.com/maps/place/Pandan+Indah,+Kuala+Lumpur,+Selangor/@3.1311177,101.7523725,16z/data=!4m5!3m4!1s0x31cc365f86dd4897:0xdb6d184b895e07c7!8m2!3d3.133892!4d101.7516751" target="_blank">https://www.google.com/maps/place/Pandan+Indah,+Kuala+Lumpur,+Selangor/@3.1311177,101.7523725,16z/data=!4m5!3m4!1s0x31cc365f86dd4897:0xdb6d184b895e07c7!8m2!3d3.133892!4d101.7516751</a>, accessed on 10 November 2020).</p> Full article ">Figure 4
<p>Routes followed in the mobile testing around the area of Pandan Indah, on 24 November 2020. (Source: Google Maps available at <a href="https://www.google.com/maps/place/Pandan+Indah,+Kuala+Lumpur,+Selangor/@3.1311177,101.7523725,16z/data=!4m5!3m4!1s0x31cc365f86dd4897:0xdb6d184b895e07c7!8m2!3d3.133892!4d101.7516751" target="_blank">https://www.google.com/maps/place/Pandan+Indah,+Kuala+Lumpur,+Selangor/@3.1311177,101.7523725,16z/data=!4m5!3m4!1s0x31cc365f86dd4897:0xdb6d184b895e07c7!8m2!3d3.133892!4d101.7516751</a>, accessed on 10 November 2020).</p> Full article ">Figure 5
<p>Prototype (<b>a</b>) Internal Connection. (<b>b</b>) External case.</p> Full article ">Figure 6
<p>The flow of the system.</p> Full article ">Figure 7
<p>Internal Architecture of the Wireless Outdoor Individual Exposure Indicator System Prototype.</p> Full article ">Figure 8
<p>Connectivity of the individual outdoor exposure indicator using wireless system.</p> Full article ">Figure 9
<p>Cloud system used by the prototype.</p> Full article ">Figure 10
<p>Wireless Outdoor Individual Exposure Indicator System display on different platforms. (<b>a</b>) Display on a website. (<b>b</b>) Display on smartphone application.</p> Full article ">Figure 10 Cont.
<p>Wireless Outdoor Individual Exposure Indicator System display on different platforms. (<b>a</b>) Display on a website. (<b>b</b>) Display on smartphone application.</p> Full article ">Figure 11
<p>Temporal distribution of PM<sub>2.5</sub> during the testing.</p> Full article ">Figure 12
<p>Hourly average of PM<sub>2.5</sub> during the mobile test run.</p> Full article ">Figure 13
<p>Daily average of PM<sub>2.5</sub> mass concentration for the prototype and the DustTrak.</p> Full article ">Figure 14
<p>The smartphone display messages (<b>a</b>) in Malay language, and (<b>b</b>) in English Language.</p> Full article ">Figure 15
<p>Hourly average of PM<sub>2.5</sub> mass concentration.</p> Full article ">Figure 16
<p>Daily average of NO<sub>2</sub> mass concentration.</p> Full article ">Figure 17
<p>Daily average of CO mass concentration.</p> Full article ">Figure 18
<p>Regression of pollutant concentrations PM<sub>2.5</sub> prototype compared to DustTrak reference monitors. The linear regression equation is issued.</p> Full article ">
16 pages, 6608 KiB  
Review
Effect of Nanomaterials on Gut Microbiota
by Ying Ma, Jiahe Zhang, Nairui Yu, Jiaqi Shi, Yi Zhang, Zhangjian Chen and Guang Jia
Toxics 2023, 11(4), 384; https://doi.org/10.3390/toxics11040384 - 17 Apr 2023
Cited by 5 | Viewed by 2616
Abstract
Nanomaterials are widely employed in everyday life, including food and engineering. Food additives on a nanoscale can enter the body via the digestive tract. The human gut microbiota is a dynamically balanced ecosystem composed of a multitude of microorganisms that play a crucial [...] Read more.
Nanomaterials are widely employed in everyday life, including food and engineering. Food additives on a nanoscale can enter the body via the digestive tract. The human gut microbiota is a dynamically balanced ecosystem composed of a multitude of microorganisms that play a crucial role in maintaining the proper physiological function of the digestive tract and the body’s endocrine coordination. While the antibacterial capabilities of nanomaterials have received much interest in recent years, their impacts on gut microbiota ought to be cautioned about and explored. Nanomaterials exhibit good antibacterial capabilities in vitro. Animal studies have revealed that oral exposure to nanomaterials inhibits probiotic reproduction, stimulates the inflammatory response of the gut immune system, increases opportunistic infections, and changes the composition and structure of the gut microbiota. This article provides an overview of the impacts of nanomaterials, particularly titanium dioxide nanoparticles (TiO2 NPs), on the gut microbiota. It advances nanomaterial safety research and offers a scientific foundation for the prevention, control, and treatment of illnesses associated with gut microbiota abnormalities. Full article
(This article belongs to the Special Issue Toxicity and Mechanisms of Occupational and Environmental Pollutants)
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<p>The provision of various antibacterial mechanisms by nanoparticles. Nanoparticles and the ions they release produce free radicals that induce oxidative stress, which induces bacterial death. (<b>A</b>) Reproduced with permission [<a href="#B31-toxics-11-00384" class="html-bibr">31</a>]. Copyright 2012, Elsevier. (<b>B</b>) “?” represented that there is no consensus on the signal of bacterial death caused by nanomaterials. Reproduced with permission [<a href="#B41-toxics-11-00384" class="html-bibr">41</a>]. Copyright 2017, Elsevier.</p> Full article ">Figure 2
<p>Titanium dioxide causes oxidative stress, which has an antimicrobial effect. (<b>A</b>) TiO<sub>2</sub> NPs generate reactive oxygen during the photocatalytic reduction and oxidation of oxygen and water. Reproduced with permission [<a href="#B52-toxics-11-00384" class="html-bibr">52</a>]. Copyright 2017, American Chemical Society. (<b>B</b>) Damage of TiO<sub>2</sub> NPs to <span class="html-italic">E. coli</span> and <span class="html-italic">S. aureus</span>. Reproduced with permission [<a href="#B53-toxics-11-00384" class="html-bibr">53</a>]. Copyright 2019, MDPI. (<b>C</b>) Scanning electron microscopy images of <span class="html-italic">E. coli</span> bacterial cells exposed to TiO<sub>2</sub> NPs at various concentrations (0.01, 0.1, and 1.0 mg/mL). The initial bacterial concentration was 10<sup>6</sup>. Reproduced with permission [<a href="#B54-toxics-11-00384" class="html-bibr">54</a>]. Copyright 2016, <span class="html-italic">Nature</span>.</p> Full article ">Figure 3
<p>Effects of Ag NPs on gut microbiota. (<b>A</b>,<b>B</b>) The TEM images of <span class="html-italic">E. coli</span> co-incubated with Ag NPs. Reproduced with permission [<a href="#B64-toxics-11-00384" class="html-bibr">64</a>]. Copyright 2015, American Chemical Society. (<b>C</b>) Mechanisms of Ag NPs’ impact on bacterial cells. Reproduced with permission [<a href="#B65-toxics-11-00384" class="html-bibr">65</a>]. Copyright 2018, Elsevier.</p> Full article ">Figure 4
<p>Effects of ZnO NPs on gut microbiota. The SEM (<b>A</b>,<b>B</b>) and TEM (<b>D</b>,<b>E</b>) images of <span class="html-italic">E. coli</span> treated without ZnO NPs (<b>A</b>,<b>D</b>) and 20 mM ZnO NPs (<b>B</b>,<b>E</b>). White arrows indicate ZnO NPs. Scanning electron microscopy scale bar = 1 μm, TEM scale bar = 0.2 μm. Reproduced with permission [<a href="#B79-toxics-11-00384" class="html-bibr">79</a>]. Copyright 2021, MDPI. (<b>C</b>) ZnO NP antibacterial mechanism and influencing factors schematic diagram. Reproduced with permission [<a href="#B80-toxics-11-00384" class="html-bibr">80</a>]. Copyright 2020, Dovepress.</p> Full article ">Figure 5
<p>Atomic force microscopy and 3D images of <span class="html-italic">E. coli</span> cells after incubation with graphene oxide (GO). Incubate <span class="html-italic">E. coli</span> with deionized water (<b>A</b>,<b>B</b>), 40 μg/mL GO-0 (<b>C</b>,<b>D</b>) and 40 μg/mL GO-240 (<b>E</b>,<b>F</b>) for 2 h. Scale bar is 1 μm. Reproduced with permission [<a href="#B94-toxics-11-00384" class="html-bibr">94</a>]. Copyright 2012, American Chemical Society. (<b>G</b>,<b>H</b>) Scanning electron microscopy images of <span class="html-italic">E. coli</span> incubated with laser-induced graphene (LIG) 1 and 8 h. Scale bar is 10 μm. Reproduced with permission [<a href="#B95-toxics-11-00384" class="html-bibr">95</a>]. Copyright 2020, American Chemical Society.</p> Full article ">
10 pages, 1123 KiB  
Article
Reasons, Form of Ingestion and Side Effects Associated with Consumption of Amanita muscaria
by Michal Ordak, Aleksandra Galazka, Tadeusz Nasierowski, Elzbieta Muszynska and Magdalena Bujalska-Zadrozny
Toxics 2023, 11(4), 383; https://doi.org/10.3390/toxics11040383 - 17 Apr 2023
Cited by 3 | Viewed by 10272
Abstract
In recent months, there has been a new trend involving the consumption of Amanita muscaria. The aim of this article was to investigate the reasons for consumption, the form taken and the adverse symptoms that were indicated by those consuming Amanita muscaria [...] Read more.
In recent months, there has been a new trend involving the consumption of Amanita muscaria. The aim of this article was to investigate the reasons for consumption, the form taken and the adverse symptoms that were indicated by those consuming Amanita muscaria. After analysing 5600 comments, 684 people were included in the study, who, in social media groups such as Facebook, stated the purpose of consuming the mushroom (n = 250), the form of mushroom they were taking (n = 198) or the adverse symptoms they experienced (n = 236). The gender of the subjects differentiated the parameters analysed. In the study group of women, the main purpose of consuming Amanita muscaria was to reduce pain, as well as to reduce skin problems, while in men it was mainly to relieve stress, reduce the severity of depressive symptoms and reduce insomnia (p < 0.001). With regard to the form of mushroom ingested, tincture was predominant in the women’s study group, while dried was predominant in the men (p < 0.001). In terms of side effects, women reported primarily headaches, while men reported nausea, vomiting, abdominal pain and drowsiness (p < 0.001). Advanced research on Amanita muscaria should be carried out to make the community aware of the toxicity of this fungus. Full article
(This article belongs to the Special Issue Holistic Toxicological Approaches in Forensic Sciences Applications: New Perspectives and Approaches to Improve Casework)
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<p>Reasons for consuming <span class="html-italic">Amanita muscaria</span> in the study group women and men.</p> Full article ">Figure 2
<p>Form of consumption of <span class="html-italic">Amanita muscaria</span> in the study group women and men.</p> Full article ">Figure 3
<p>Adverse effects related to the consumption of <span class="html-italic">Amanita muscaria</span> in the study group women and men.</p> Full article ">
15 pages, 2977 KiB  
Article
Spatial Distribution and Risk Assessment of Antibiotics in 15 Pharmaceutical Plants in the Pearl River Delta
by Yuanfei Liu, Xiaoxia Shi, Xiaoxia Chen, Ping Ding, Lijuan Zhang, Jian Yang, Jun Pan, Yunjiang Yu, Jinhua Wu and Guocheng Hu
Toxics 2023, 11(4), 382; https://doi.org/10.3390/toxics11040382 - 17 Apr 2023
Cited by 1 | Viewed by 1688
Abstract
Pharmaceutical plants are an essential source of antibiotics emitted into the aqueous environment. The monitoring of target antibiotics in pharmaceutical plants through various regions is vital to optimize contaminant release. The occurrence, distribution, removal, and ecological risk of 30 kinds of selected antibiotics [...] Read more.
Pharmaceutical plants are an essential source of antibiotics emitted into the aqueous environment. The monitoring of target antibiotics in pharmaceutical plants through various regions is vital to optimize contaminant release. The occurrence, distribution, removal, and ecological risk of 30 kinds of selected antibiotics in 15 pharmaceutical plants in the Pearl River Delta (PRD) were investigated in this study. Lincomycin (LIN) showed the highest concentration (up to 56,258.3 ng/L) in the pharmaceutical plant influents from Zhongshan city. Norfloxacin (NFX) showed a higher detection frequency than other antibiotics. In addition, the spatial distribution of antibiotics in pharmaceutical plants showed significant differences, with higher concentrations of total antibiotics found in pharmaceutical plant influents in Shenzhen City than those of different regions in PRD. The treatment processes adopted by pharmaceutical plants were commonly ineffective in removing antibiotics, with only 26.7% of antibiotics being effectively removed (average removal greater than 70%), while 55.6% of antibiotics had removal rates of below 60%. The anaerobic/anoxic/oxic (AAO)-membrane bioreactor (MBR) combined process exhibited better treatment performance than the single treatment process. Sulfamethoxazole (SMX), ofloxacin (OFL), erythromycin-H2O (ETM-H2O), sulfadiazine (SDZ), sulfamethazine (SMZ), norfloxacin (NFX), and ciprofloxacin (CIP) in pharmaceutical plant effluents posed high or moderate ecological risk and deserve particular attention. Full article
(This article belongs to the Section Emerging Contaminants)
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<p>Concentration and distribution of antibiotics in influents samples from 12 pharmaceutical plants of China. (<b>a</b>): map of sampling locations. (<b>b</b>): the concentration of antibiotics in influent of Guangzhou pharmaceutical plants. (<b>c</b>): the concentration of antibiotics in influent of Foshan pharmaceutical plants. (<b>d</b>): the concentration of antibiotics in influent of Zhongshan pharmaceutical plants. (<b>e</b>): the concentration of antibiotics in influent of Shenzhen pharmaceutical plants. (<b>f</b>): the concentration of antibiotics in influent of Zhuhai pharmaceutical plants. (<b>g</b>): the total antibiotics concentration in pharmaceutical plants influent. (Abbreviations: SAs: sulfonamides; FQs: fluoroquinolones; MLs: macrolides; and TCs: tetracyclines) A–O: pharmaceutical plants A–O respectively.</p> Full article ">Figure 2
<p>Composition profiles of different antibiotics in influent, effluent, and excess sludge from 15 pharmaceutical plants of China (Abbreviations: SAs: sulfonamides; FQs: fluoroquinolones; MLs: macrolides; and TCs: tetracyclines).</p> Full article ">Figure 3
<p>Correlation between the total concentration of 30 target antibiotics and the population served by the pharmaceutical plants, GDP per capita, water consumption per capita, and pharmaceutical usage amount per day in the regions with pharmaceutical plants.</p> Full article ">Figure 4
<p>Removal efficiencies of 30 individual antibiotics in the pharmaceutical plants (Abbreviations: SDZ: Sulfadiazine; SPD: Sulfapyridine; TMP: Trimethoprim; SMZ: Sulfamethazine; SM: Sulfameter; SMM: Sulfamonomethoxine; SCP: Sulfachlorpyridazine; SMX: Sulfamethoxazole; SA: Sulfadoxine; SQX: Sulfaquinoxaline; SDM: Sulfadimethoxine; SCT: Sulfacetamide; STZ: Sulfathiazole; MAR: Marbofloxacin; NFX: Norfloxacin; OFL: Ofloxacin; CIP: Ciprofloxacin; EFX: Enrofloxacin; PEF: Pefloxacin; LIN: Lincomycin; ETM-H<sub>2</sub>O: Erythromycin-H<sub>2</sub>O; CTM: Clarithromycin; RTM: Roxithromycin; OTC: Oxytetracycline; TC: Tetracycline; CTC: Chlorotetracycline; and DC: Doxycycline).</p> Full article ">Figure 5
<p>Mean removal efficiencies (%) of antibiotics in pharmaceutical plants with different treatment processes (Abbreviations: AO: anaerobic/aerobic; CASS: conventional activated sludge system; AAO: anaerobic/anoxic/aerobic; MBR: membrane bioreactor; and AAO + MBR: anaerobic/anoxic/aerobic and membrane bioreactor).</p> Full article ">Figure 6
<p>Risk quotients (RQs) for 27 target antibiotics in the pharmaceutical plant effluents (Abbreviations: SDZ: Sulfadiazine; SPD: Sulfapyridine; TMP: Trimethoprim; SMZ: Sulfamethazine; SM: Sulfameter; SMM: Sulfamonomethoxine; SCP: Sulfachlorpyridazine; SMX: Sulfamethoxazole; SA: Sulfadoxine; SQX: Sulfaquinoxaline; SDM: Sulfadimethoxine; SCT: Sulfacetamide; STZ: Sulfathiazole; MAR: Marbofloxacin; NFX: Norfloxacin; OFL: Ofloxacin; CIP: Ciprofloxacin; EFX: Enrofloxacin; PEF: Pefloxacin; LIN: Lincomycin; ETM-H<sub>2</sub>O: Erythromycin-H<sub>2</sub>O; CTM: Clarithromycin; RTM: Roxithromycin; OTC: Oxytetracycline; TC: Tetracycline; CTC: Chlorotetracycline; and DC: Doxycycline).</p> Full article ">
16 pages, 6579 KiB  
Article
Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats
by Mohamed Moharram Badawy, Mohamed Z. Sayed-Ahmed, Yosif Almoshari, Saad S. Alqahtani, Saeed Alshahrani, Heba Allah Ali Mabrouk, Marwa M. Abd-Elsalam, Khalid Alkashif, Sarfaraz Ahmad, Ahmed M. El-Sebaey, Mohamed G. Hamama and Dalia Alsaied Moustafa Ahmed
Toxics 2023, 11(4), 381; https://doi.org/10.3390/toxics11040381 - 17 Apr 2023
Cited by 2 | Viewed by 2407
Abstract
Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the [...] Read more.
Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values. Full article
(This article belongs to the Section Novel Methods in Toxicology Research)
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Full article ">Figure 1
<p>Representative hydrodynamic size (<b>A</b>) and Zeta potential (<b>B</b>) of the SiNP suspension.</p> Full article ">Figure 2
<p>Representative liver sections photomicrographs. (<b>A1</b>,<b>A2</b>) Liver of the control rats. (<b>B1</b>,<b>B2</b>) Rats that received Mg. (<b>C1</b>,<b>C2</b>) Rats exposed to SiNPs showing sinusoidal dilatation (arrowheads). The hepatocytes’ nuclei are of variable size with pyknosis of some nuclei (arrows). Most of the hepatocytes show cytoplasmic vacuolation (tailed arrows). (<b>D1</b>,<b>D2</b>) Rats exposed to SiNPs and received Mg, showing no obvious changes in the hepatocytes and hepatic sinusoids. H&amp;E. (<b>A1</b>,<b>B1</b>,<b>C1</b>,<b>D1</b>) ×20 magnification. (<b>A2</b>,<b>B2</b>,<b>C2</b>,<b>D2</b>) ×40 magnification.</p> Full article ">Figure 3
<p>Representative kidney section photomicrographs. (<b>A1</b>,<b>A2</b>) Control rats demonstrating the normal structure of the glomeruli (G), proximal (P), and distal (D) convoluted tubules. (<b>B1</b>,<b>B2</b>) Rata that received Mg. (<b>C1</b>,<b>C2</b>) Rats exposed to SiNPs showing inter-tubular congestion (arrows) with swelling and vacuolation of the endothelial lining of the proximal and distal convoluted tubules (arrow heads). (<b>D1</b>,<b>D2</b>) Rats exposed to SiNPs and that received Mg showing normal cellularity of the glomerulus and renal tubules. H&amp;E. (<b>A1</b>,<b>B1</b>,<b>C1</b>,<b>D1</b>) ×20 magnification. (<b>A2</b>,<b>B2</b>,<b>C2</b>,<b>D2</b>) ×40 magnification.</p> Full article ">Figure 4
<p>Representative adrenal gland sections photomicrographs. (<b>A1</b>,<b>A2</b>,<b>A3</b>) Control rats demonstrating the normal structure of the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR), and medulla (M). (<b>B1</b>,<b>B2</b>,<b>B3</b>). Rats that received Mg and showing normal histological architecture and arrangement of cells within the adrenal cortex and medulla. (<b>C1</b>,<b>C2</b>,<b>C3</b>) Rats exposed to SiNPs showing disorganized cell cords interspersed with distended blood sinusoids (arrow heads) and abnormal cortical cells, which show vacuolated cytoplasm (arrows) and pyknotic nuclei (tailed arrows). H&amp;E. (<b>A1</b>,<b>B1</b>,<b>C1</b>,<b>D1</b>) ×20 magnification. (<b>A2</b>,<b>B2</b>,<b>C2</b>,<b>D2</b>) ×40 magnification. (<b>A3</b>,<b>B3</b>,<b>C3</b>,<b>D3</b>) ×100 magnification.</p> Full article ">
17 pages, 1513 KiB  
Review
Advances in the Utilization of Zebrafish for Assessing and Understanding the Mechanisms of Nano-/Microparticles Toxicity in Water
by Pengyu Lei, Wenxia Zhang, Jiahui Ma, Yuping Xia, Haiyang Yu, Jiao Du, Yimeng Fang, Lei Wang, Kun Zhang, Libo Jin, Da Sun and Junbo Zhong
Toxics 2023, 11(4), 380; https://doi.org/10.3390/toxics11040380 - 17 Apr 2023
Cited by 11 | Viewed by 2624
Abstract
A large amount of nano-/microparticles (MNPs) are released into water, not only causing severe water pollution, but also negatively affecting organisms. Therefore, it is crucial to evaluate MNP toxicity and mechanisms in water. There is a significant degree of similarity between the genes, [...] Read more.
A large amount of nano-/microparticles (MNPs) are released into water, not only causing severe water pollution, but also negatively affecting organisms. Therefore, it is crucial to evaluate MNP toxicity and mechanisms in water. There is a significant degree of similarity between the genes, the central nervous system, the liver, the kidney, and the intestines of zebrafish and the human body. It has been shown that zebrafish are exceptionally suitable for evaluating the toxicity and action mechanisms of MNPs in water on reproduction, the central nervous system, and metabolism. Providing ideas and methods for studying MNP toxicity, this article discusses the toxicity and mechanisms of MNPs from zebrafish. Full article
(This article belongs to the Special Issue Toxicity and Health Effects of Environmental Nano-/Microparticle Exposure)
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Graphical abstract

Graphical abstract
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<p>The zebrafish can be used for toxicity evaluation and mechanistic studies of the nervous, reproductive, and immune systems of MNPs.</p> Full article ">Figure 2
<p>Advantages of zebrafish for toxicity evaluation of MNPs. (<b>A</b>) The blood–brain barrier, central nervous system, and social behavior are similar to those of humans, making it an ideal animal model for studying neurotoxicity; (<b>B</b>) The intestine, liver and kidney are similar to those of humans, which makes them suitable for studying MNPs metabolism and immune diseases; (<b>C</b>) The reproductive and developmental toxicity of MNPs can be easily studied due to the short reproductive cycle of zebrafish and the large number of eggs laid. In addition, the embryos are transparent, so a microscope can be used to observe the cell division and organ formation process; (<b>D</b>) The genome of zebrafish has been fully sequenced, and is highly consistent with the human genome, and can be easily manipulated by genetic manipulation such as gene knockout and gene overexpression.</p> Full article ">Figure 3
<p>Evaluation index of MNP toxicity in zebrafish in a water body. (<b>A</b>) Evaluation of the toxicity of MNPs on growth and reproduction by the damage and apoptosis of sperm, testis, and oocytes of adult zebrafish, as well as the increased rate of malformation and mortality of embryos [<a href="#B40-toxics-11-00380" class="html-bibr">40</a>,<a href="#B41-toxics-11-00380" class="html-bibr">41</a>,<a href="#B42-toxics-11-00380" class="html-bibr">42</a>]; (<b>B</b>) Evaluation of the behavioral and neurological toxicity of MNPs by increasing oxidative-stress level and apoptosis in the zebrafish brain, as well as behavioral experiments to detect memory, learning, and mental disorders in zebrafish [<a href="#B43-toxics-11-00380" class="html-bibr">43</a>,<a href="#B44-toxics-11-00380" class="html-bibr">44</a>,<a href="#B45-toxics-11-00380" class="html-bibr">45</a>]; (<b>C</b>) Evaluation of the toxicity of MNPs on the metabolism and immune system by the upregulation of immune-related gene expression and apoptosis, as well as the reduction of hepatic glucose and lipid metabolism, glucose, α-ketoglutarate, and lipid-related indicators [<a href="#B46-toxics-11-00380" class="html-bibr">46</a>,<a href="#B47-toxics-11-00380" class="html-bibr">47</a>,<a href="#B48-toxics-11-00380" class="html-bibr">48</a>].</p> Full article ">Figure 4
<p>Diagram of the toxicological mechanism of MNPs in water explored using zebrafish. (<b>A</b>) The mechanism of central nervous toxicity of MNPs: Excessive production of H<sub>2</sub>O<sub>2</sub>, inactivation of enzyme protein, disruption of the balance between CAT and SOD activities, inhibition of AChE activity, and significant reduction in the activity of GS and GDH, leading to brain neurodegeneration. (<b>B</b>) Mechanism of reproductive toxicity of MNPs: MNPs were transferred to oocytes of adult female zebrafish, causing reduction of GR and GSH contents, leading to oxidative stress in oocytes. At the same time, NF-b and TNF- expression was significantly upregulated, affecting the offspring’s growth and development. (<b>C</b>) Effect of MNPs on zebrafish gut: Increased abundance of Fusobacterium metabolized mucin into short-chain fatty butyrate and induce intestinal inflammation in zebrafish. The number of actinobacteria decreased, foreign bodies accumulated in the intestine, and the number of Firmicutes decreased, all of which resulted in reduced mucus production and damage to the intestinal barrier. (<b>D</b>) The mechanism of metabolic toxicity of MNPs: Reduction of PEP, GK, and PK in the glycolytic pathway led to insufficient glucose and pyruvate production, leading to disorders of glucose metabolism. Additionally, the expression levels of <span class="html-italic">PPAR</span>, <span class="html-italic">ACC1</span>, <span class="html-italic">FAS</span>, <span class="html-italic">FABP6</span>, <span class="html-italic">ACO</span>, <span class="html-italic">CPT1</span>, <span class="html-italic">acat2</span>, <span class="html-italic">ALDH9a1a</span>, <span class="html-italic">ALDH2b</span>, and <span class="html-italic">echs1</span> genes were reduced, resulting in abnormal lipid metabolism.</p> Full article ">Figure 5
<p>Solutions to the limitations of zebrafish. (<b>A</b>) To optimize the zebrafish exposure experiments, larval or adult zebrafish should be exposed to real MNPs in contaminated water. (<b>B</b>) The current unified experimental operating procedures and standards must be strictly followed, and researchers still need to promote the construction of standards, so that the toxicity evaluation of zebrafish as a model organism can be more perfect. (<b>C</b>) The mutual verification mechanism for animal models must be strengthened. (<b>D</b>) Long-term exposure experiments should be carried out to expose adult zebrafish to MNPs over a long period of time and there should be generation studies from adult fish to offspring, and then to offspring adult respawning to comprehensively investigate MNP toxic mechanisms.</p> Full article ">
17 pages, 2565 KiB  
Article
Natural Polyphenols—Resveratrol, Quercetin, Magnolol, and β-Catechin—Block Certain Aspects of Heroin Addiction and Modulate Striatal IL-6 and TNF-α
by Shaimaa ElShebiney, Rania Elgohary, Marwa El-Shamarka, Noha Mowaad and Osama A. Abulseoud
Toxics 2023, 11(4), 379; https://doi.org/10.3390/toxics11040379 - 17 Apr 2023
Cited by 3 | Viewed by 2162
Abstract
We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for [...] Read more.
We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for 14 consecutive days. The rats were treated with distilled water (1 mL), quercetin (50 mg/kg/d), β-catechin (100 mg/kg/d), resveratrol (30 mg/kg/d), or magnolol (50 mg/kg/d) through oral gavage for 7 consecutive days, 30 min before heroin administration, starting on day 8. Heroin withdrawal manifestations were assessed 24 h post last heroin administration following the administration of naloxone (1 mg/kg i.p). Heroin CPP reinstatement was tested following a single dose of heroin (10 mg/kg i.p.) administration. Striatal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were quantified (ELISA) after naloxone-precipitated heroin withdrawal. Compared to the vehicle, the heroin-administered rats spent significantly more time in the heroin-paired chamber (p < 0.0001). Concomitant administration of resveratrol and quercetin prevented the acquisition of heroin CPP, while resveratrol, quercetin, and magnolol blocked heroin-triggered reinstatement. Magnolol, quercetin, and β-catechin blocked naloxone-precipitated heroin withdrawal and increased striatal IL-6 concentration (p < 0.01). Resveratrol administration was associated with significantly higher withdrawal scores compared to those of the control animals (p < 0.0001). The results of this study show that different polyphenols target specific behavioral domains of heroin addiction in a CPP model and modulate the increase in striatal inflammatory cytokines TNF-α and IL-6 observed during naloxone-precipitated heroin withdrawal. Further research is needed to study the clinical utility of polyphenols and to investigate the intriguing finding that resveratrol enhances, rather than attenuates naloxone-precipitated heroin withdrawal. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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<p>Study design: (<b>A</b>) naloxone-precipitated opiate withdrawal cohort; (<b>B</b>) heroin-triggered reinstatement cohort.</p> Full article ">Figure 2
<p>Heroin CPP acquisition is blocked by resveratrol and quercetin.</p> Full article ">Figure 3
<p>(<b>A</b>) Magnolol attenuates naloxoneprecipitated heroin withdrawal: magnolol blocked naloxone-precipitated heroin withdrawal. One-way ANOVA F(6, 42) = 70.51, <span class="html-italic">p</span> &lt; 0.0001 [mean difference between heroin control and naloxone+ magnolol = −1.446, 95% CI = −4.412 to 1.519, <span class="html-italic">p</span> = 0.6]. Resv, Quer, and Cat all are associated with significantly higher withdrawal scores compared to those of the control animals (<span class="html-italic">p</span> &lt; 0.0001 for Resv and Quer and <span class="html-italic">p</span> = 0.003 for Cat). Resv specifically caused more opiate withdrawal, even more than spontaneous and naloxone-precipitated withdrawals [mean difference in withdrawal scores between Resv and heroin control = −18.3, between spontaneous WD and heroin control = −7.5, and between naloxone-precipitated WD and heroin control = −12.9, according to one way ANOVA, followed by Dunnett’s multiple comparisons test against Her + Veh control group, n = 6–10 animals per group (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001). (<b>B</b>) Magnolol, quercetin, and β-catechin prevented the rapid wight loss associated with naloxone-precipitated heroin withdrawal: significant weight loss during naloxone-precipitated opiate withdrawal according to one-way ANOVA F(5, 33) = 4.605, <span class="html-italic">p</span> = 0.002 [mean difference in % body weight between heroin control and naloxone-precipitated withdrawal = 3.180, 95% CI = 0.6483 to 5.712, <span class="html-italic">p</span> = 0.009]. Mag [mean difference in % body weight between heroin control and naloxone-precipitated withdrawal + magnolol = 1.629, 95% CI = −0.9795 to 4.237, <span class="html-italic">p</span> = 0.3], Quer [mean difference in % body weight between heroin control and naloxone-precipitated withdrawal+ quercetin = 2.648, 95% CI = −0.05820 to 5.355, <span class="html-italic">p</span> = 0.056], and Cat [mean difference in % body weight between heroin control and naloxone-precipitated withdrawal + catechin = 0.6467, 95% CI = −2.060 to 3.353, <span class="html-italic">p</span> = 0.9] prevented weight loss, while Resv was associated with significant weight loss [mean difference in % body weight between heroin control and naloxone-precipitated withdrawal+ resveratrol = 3.973, 95% CI = 1.267 to 6.680, <span class="html-italic">p</span> = 0.002] by one way ANOVA followed by Dunnett’s multiple comparisons test against Her + Veh control group, n = 6–10 animals per group (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001). (<b>C</b>) Heroin administration did not cause reduction in voluntary locomotor activity as measured in an open field: One-way ANOVA F(5, 45)= 11.16, <span class="html-italic">p</span> &lt; 0.0001 [Veh + Veh vs. Her + Veh mean difference = 19.70, 95% CI = −7.256 to 46.66, <span class="html-italic">p</span> = 0.2]. However, both Resv [Veh + Veh vs. Her + Resv mean difference = 30.81, 95% CI = 4.700 to 56.92, <span class="html-italic">p</span> = 0.01] and cat [Veh + Veh vs. Her + Cat mean difference = 48.83, 95% CI = 21.87 to 75.78, <span class="html-italic">p</span> = 0.0001] caused significant reduction in distance traveled by one way ANOVA followed by Dunnett’s multiple comparisons test against Her + Veh control group, n = 6–10 animals per group (* <span class="html-italic">p</span> &lt; 0.1, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001). (<b>D</b>) Magnolol and quercetin reduce anxiety-like behavior during naloxone-precipitated withdrawal as measured by time spent in open arm of elevated plus maze: Naloxone-precipitated withdrawal is associated with significant reduction in time spent in open arm compared to heroin controls by one-way ANOVA F(5, 42) = 34.75, <span class="html-italic">p</span> &lt; 0.0001, [mean difference in time between heroin control and naloxone-precipitated withdrawal = 87.86, 95% CI = 29.41 to 146.3, <span class="html-italic">p</span> = 0.001]. Mag [mean difference in time between heroin control and naloxone-precipitated withdrawal + Mag = 14.88, 95% CI = −45.27 to 75.02, <span class="html-italic">p</span> = 0.9] and Quer [mean difference in time between heroin control and naloxone-precipitated withdrawal + Quer −6.125, 95% CI = −54.02 to 66.27, <span class="html-italic">p</span> = 0.9] increased the time in open arm to be non-significantly different from heroin control animals. However, Resv [mean difference in time between heroin control and naloxone-precipitated withdrawal + Resv = −148.3, 95% CI = −210.5 to −85.99, <span class="html-italic">p</span> &lt; 0.0001] and Cat [mean difference in time between heroin control and naloxone-precipitated withdrawal + Cat = −148.3, 95% CI = −208.4 to −88.10, <span class="html-italic">p</span> &lt; 0.0001] were associated with a significant increase in open arm time compared to controls by one way ANOVA followed by Dunnett’s multiple comparisons test against Her + Veh control group, n = 6–8 animals per group. (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001). (<b>E</b>) Quercetin, magnolol, and β-catechin attenuate heroin-induced sucrose preference: Heroin administration was associated with significant increase in sucrose preference test by one-way ANOVA [F(5, 30) = 4.300, <span class="html-italic">p</span> = 0.004, heroin vs. vehicle mean difference = 15.84, 95% CI = 28.18 to 3.495, <span class="html-italic">p</span> = 0.008]. Resv did not reduce the increase in heroin-induced sucrose preference Resv vs. Vehicle mean difference = 14.44, 95% CI = 26.78 to 2.092, <span class="html-italic">p</span> = 0.017]. Quer, Mag and Cat, on the other hand attenuated heroin-induced increase in sucrose preference by one way ANOVA followed by Dunnett’s multiple comparisons test against Her + Veh control group, n = 8–10 animals per group (* <span class="html-italic">p</span> &lt; 0.1, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001).</p> Full article ">Figure 4
<p>Resveratrol, quercetin, and magnolol prevent heroin-triggered reinstatement.</p> Full article ">Figure 5
<p>The effect of polyphenols on striatal TNF α and IL-6 and concentration. (<b>A</b>) Resveratrol and magnolol attenuate heroin-induced increase in striatal TNF-α concentration: Significant differences in striatal TNF-α concentrations were evident by one-way ANOVA [F(4, 15) = 6.885, <span class="html-italic">p</span> &lt; 0.01]. Dunnett’s multiple comparisons test against Her + Veh control group (n = 4) showed significant effect of resveratrol [mean difference in striatal TNF-α concentration between heroin and heroin+ resveratrol groups = 187.4, 95% CI = 81.40 to 293.4, <span class="html-italic">p</span> &lt; 0.001], and magnolol [mean difference in striatal TNF-α concentration between heroin and heroin+ magnolol groups = 155.9, 95% CI = 49.84 to 261.9, <span class="html-italic">p</span> &lt; 0.01] on TNF-α concentration. (<b>B</b>) Resveratrol and β-catechin attenuate, while quercetin accentuates, heroin-induced increase in striatal IL-6 concentration: Significant differences in striatal IL-6 concentrations were evident by one-way ANOVA [F(4, 15) = 42.74, <span class="html-italic">p</span> &lt; 0.0001]. Dunnett’s multiple comparisons test against Her + Veh control group (n = 4) showed significant effect of resveratrol [mean difference in striatal IL-6 concentration between heroin and heroin+ resveratrol groups = 51.11, 95% CI = 18.24 to 83.98, <span class="html-italic">p</span> &lt; 0.01], quercetin [mean difference in striatal IL-6 concentration between heroin and heroin + quercetin groups = −74.66, 95% CI = −107.5 to −41.78, <span class="html-italic">p</span> &lt; 0.0001], and β-catechin [mean difference in striatal IL-6 concentration between heroin and heroin+ β-catoctin groups = 68.69, 95% CI = 35.82 to 101.6, <span class="html-italic">p</span> &lt; 0.001] on IL-6 concentration (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001).</p> Full article ">
15 pages, 1076 KiB  
Article
Quantitation and Stability of Nicotine in Canadian Vaping Liquids
by Ivana Kosarac, Guru P. Katuri, Cariton Kubwabo, Shabana Siddique and Trevor K. Mischki
Toxics 2023, 11(4), 378; https://doi.org/10.3390/toxics11040378 - 17 Apr 2023
Cited by 1 | Viewed by 2562
Abstract
Electronic cigarettes (e-cigarettes, vaping products) have become increasingly popular, with recent increases in use associated with closed systems delivering higher concentrations of nicotine. Most vaping products designed as an alternative to combustible cigarettes contain nicotine. A number of published studies have examined the [...] Read more.
Electronic cigarettes (e-cigarettes, vaping products) have become increasingly popular, with recent increases in use associated with closed systems delivering higher concentrations of nicotine. Most vaping products designed as an alternative to combustible cigarettes contain nicotine. A number of published studies have examined the reported concentrations of nicotine in vaping liquids (e-liquids) and found discrepancies between labelled and measured levels. Some discrepancy can also be explained by the lack of stability of nicotine in these types of products. Recently, a chemical analysis method for the quantitative determination of low and high levels of nicotine in vaping liquids was developed. This method uses dilution with acetonitrile prior to analysis with gas chromatograph mass spectrometry (GC-MS) in single ion monitoring mode (SIM). The developed method was validated using a laboratory-prepared vaping liquid as well as commercially available, nicotine-free products fortified with nicotine in the laboratory. The method detection limit (MDL) and the limit of quantitation (LOQ) for nicotine were calculated to be 0.002 mg/mL and 0.006 mg/mL, respectively. The newly developed method was applied to quantify nicotine in commercially available vaping liquids of various flavour profiles and across a wide range of nicotine concentrations, including those with nicotine salts. Furthermore, a subset of vaping liquids were analyzed to elucidate nicotine stability in various product subtypes. After a period of six months of accelerated storage to mimic one year, the overall mean percent of the original nicotine concentration remaining in the salt-based vaping products was 85% (minimum 64%, maximum 99%) while in the free-base nicotine products it was 74% (minimum 31%, maximum 106%). Nicotine stability in vaping liquids was found to be influenced by the nicotine form (pH) of formulation and its chemical composition. Non-targeted, qualitative analysis of chemical composition of vaping products showed that most constituents were identified and found to be remaining in the products following stability trials; however, three new compounds were tentatively identified in some vaping liquids at the end of the stability trials. Stability studies and the accurate quantitation of nicotine in vaping products can help inform product standards related to the safety, quality and utility of vaping products as a smoking cessation tool. Full article
(This article belongs to the Special Issue Assessing Novel Tobacco Products)
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<p>Vaping liquid extracted by mass chromatogram for single ion mass monitoring, <span class="html-italic">m</span>/<span class="html-italic">z</span> 84 in (<b>A</b>) sample 0061 nicotine-free vaping liquid (floral flavour category), (<b>B</b>) sample 0084 labelled as 1.5 mg/mL nicotine vaping liquid (confectionery category).</p> Full article ">Figure 2
<p>(<b>A</b>)<b>.</b> Stability of 13C<sub>3</sub> nicotine; (<b>B</b>). Stability of <sup>12</sup>C nicotine in three lots each: vanilla, mint and fruit vaping products.</p> Full article ">Figure 3
<p>(<b>A</b>)<b>.</b> Extracted ion chromatograms of (1′S 2′S) nicotine-1′-oxide (m/z 178) and (1′S 2′S) 13C<sub>3</sub> nicotine-1′-oxide (m/z 181); (<b>B</b>)<b>.</b> Degradation and thermal rearrangement of <sup>13</sup>C<sub>3</sub> nicotine to (1′S 2′S) <sup>13</sup>C<sub>3</sub> nicotine-1′-oxide.</p> Full article ">
25 pages, 18091 KiB  
Article
Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
by Medhat Taha, Sara T. Elazab, Tourki A. S. Baokbah, Abdullah G. Al-Kushi, Mohamed Ezzat Mahmoud, Omer Abdelbagi, Naeem F. Qusty, Ibrahim El-Shenbaby, Omar Babateen, Alaa. M. Badawy and Mohie Mahmoud Ibrahim
Toxics 2023, 11(4), 377; https://doi.org/10.3390/toxics11040377 - 16 Apr 2023
Cited by 5 | Viewed by 2191
Abstract
Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has [...] Read more.
Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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Figure 1
<p>Representative photomicrograph of renal tissues from the control and experimental groups stained with H&amp;E. (<b>A</b>,<b>C</b>) The control and ZW groups show cortical glomeruli and tubules with normal architecture. (<b>B</b>,<b>D</b>) The control and ZW groups show medullary tubules with normal histology. (<b>E</b>) The CsA group shows a diffuse loss of cellular detail with hypereosinophilic cytoplasm and nuclear pyknosis, karyorrhexis, and karyolysis (necrosis) (thin arrow), along with swollen, vacuolated cytoplasm with faded nuclei beside intraluminal eosinophilic globules admixed with sloughed tubular epithelial cells, necrotic debris (granular casts) (star), and proliferative glomerular capillaries (thick arrow). (<b>F</b>) CsA medullary tubules underwent diffuse medullary tubular necrosis (thin arrow) and vacuolation (star) with focal interstitial fibrosis (thick arrow). (<b>G</b>) The CsA group shows diffuse necrotic cortical tubules with a large intraluminal hyaline cast. (<b>H</b>) Medullary tubular sloughing (thin arrow) and intraluminal hyaline cast (star) with interstitial congestion (thick arrow). (<b>I</b>) The CsA + ZW group displays occasional individual tubular necrosis (thin arrow). (<b>J</b>) The CsA + ZW group exhibits diffuse minimal-to-mild interstitial congestion (thick arrow). (<b>K</b>) Histogram of the percentage area of the histological score. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 2
<p>Photomicrograph of PAS expression in kidneys from control and experimental rats. (<b>A</b>–<b>D</b>) The control and ZW groups show PAS highlights of the glomerular basement membrane and tubular epithelium of the cortical and medullary region. (<b>E</b>,<b>F</b>) The CsA group shows PAS-positive staining in the dilated cortical and medullary tubules (arrowheads) with intraluminal proteinaceous globules (thin arrows). (<b>G</b>,<b>H</b>) The CsA + ZW group shows focal intracytoplasmic-positive PAS in the tubular epithelium of the cortex and the positive staining of the tubular basement membrane of medullary tubules (thin arrows). (<b>I</b>) Histogram of the percentage area of PAS expression. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×, bar = 50 µm.</p> Full article ">Figure 3
<p>Bax immunohistochemistry of the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show faint cytoplasmic Bax expression in normal cortical and medullary tubules. (<b>E</b>,<b>F</b>) The CsA group shows diffuse severe and strong Bax expression in the cytoplasm of necrotic, sloughed tubular cells and vacuolated cells. (<b>G</b>,<b>H</b>) The CsA + ZW group shows diffuse moderate Bax expression in cortical and medullary tubules. (<b>I</b>) Histogram of the percentage area of the immunostaining of renal Bax. *** <span class="html-italic">p</span> &lt;0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 4
<p>Immunohistochemical analysis of caspase-3 expression and localization in the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show cytoplasmic expression in the normal cortical and medullary tubular epithelium. (<b>E</b>,<b>F</b>) The CsA group shows diffuse, strong expression in the glomerulus, in the cytoplasm of necrotic and vacuolated cortical and medullary tubular cells, and in the cytoplasm of vacuolated and intraluminal cells. (<b>G</b>,<b>H</b>) The CsA + ZW group shows moderate cortical and medullary tubular expression. (<b>I</b>) Kidney caspase 3 histogram. *** <span class="html-italic">p</span> &lt; 0.001, and * <span class="html-italic">p</span> &lt; 0.05 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 5
<p>The effect of ZW on the expression of the proteins (<b>A</b>,<b>B</b>) procaspase-8, (<b>A</b>,<b>C</b>) caspase-8, (<b>A</b>,<b>D</b>) capase-9, (<b>A</b>,<b>E</b>) cytochrome C, (<b>A</b>,<b>F</b>) calpain, and (<b>A</b>,<b>G</b>) caspase-3 according to Western blotting assay. *** <span class="html-italic">p</span> &lt; 0.001, and * <span class="html-italic">p</span> &lt; 0.05 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA.</p> Full article ">Figure 6
<p>Representative Bcl2-immunohistochemistry of the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show diffuse strong expression in the normal cortical and medullary tubular epithelium. (<b>E</b>,<b>F</b>) The CsA group shows diffuse moderate expression in necrotic, sloughed tubular cells and in the cytoplasm of vacuolated and intraluminal cells. (<b>G</b>,<b>H</b>) The CsA + ZW group shows diffuse strong Bcl-2 expression in the cortical and medullary tubules. (<b>I</b>) Histogram of the percentage area of immunostaining of renal Bcl-2, *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control; <sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; bar = 50 µm.</p> Full article ">Figure 7
<p>Flow cytometry analysis of renal tubular cells stained with the apoptotic marker Annexin V as an indifferent experimental group. (<b>A</b>) Control group, (<b>B</b>) ZW group, (<b>C</b>) CsA group, and (<b>D</b>) CsA + ZW group. (<b>E</b>) Histogram of apoptotic cells. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA.</p> Full article ">Figure 8
<p>Immunohistochemical investigation of beclin-1 expression and localization in the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show strong cytoplasmic expression in cortical tubules, with mild glomerular expression and diffuse expression in the cytoplasm of medullary tubules. (<b>E</b>,<b>F</b>) The CsA group shows diffuse, faint expression in the cytoplasm of necrotic and vacuolated cortical and medullary tubular cells and in the cytoplasm of vacuolated and intraluminal cells, with faint minimal expression in the glomerulus. (<b>G</b>,<b>H</b>) The CsA + ZW group shows diffuse, high cortical and medullary tubular expression, with little glomerular expression. (<b>I</b>) Renal Becline_1 histogram percentage area. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 9
<p>Representative immunohistochemical assessment of LC3 expression in the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show none-to-few faint expressions in cortical tubules without glomerular expression and diffuse expression in the cytoplasm of medullary tubules. (<b>E</b>,<b>F</b>) The CsA group shows diffuse strong expression in the cytoplasm of necrotic, sloughed, and vacuolated cortical cells, with few glomerular expressions and a lower expression in medullary tubular cells (intraluminal sloughed cells and intraluminal cast). (<b>G</b>,<b>H</b>) The CsA+ ZW group shows diffuse cortical and medullary tubular expression with low glomerular expression. (<b>I</b>) Histogram of the percentage area of the immunostaining of renal LC3. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 10
<p>Influence of ZW on the protein expression of (<b>A</b>,<b>B</b>) P UlK-1, (<b>A</b>,<b>C</b>) Atg5, (<b>A</b>,<b>D</b>) AMPK, and (<b>A</b>,<b>E</b>) mTOR proteins according to Western blotting assay. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.001, and * <span class="html-italic">p</span> &lt; 0.05 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001vs. CsA.</p> Full article ">Figure 11
<p>Representative immunohistochemical analysis of P62 expression and localization in the kidney. (<b>A</b>–<b>D</b>) The control and ZW groups show few faint cytoplasmic expressions in the cortical tubules without glomerular expression and diffuse expression in the cytoplasm of the medullary tubules. (<b>E</b>,<b>F</b>) The CsA group shows diffuse strong expression in the cytoplasm of the necrotic and vacuolated cortical, with lower expression in the medullary tubular cells (intraluminal sloughed cells and intraluminal cast). (<b>G</b>,<b>H</b>) The CsA + ZW group shows diffuse cortical and medullary tubular expression with glomerular expression. (<b>I</b>) Histogram of the percentage area of the immunostaining of renal P62. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA. Image magnification = 400×; scale bar = 50 µm.</p> Full article ">Figure 12
<p>The effect of ZW treatment on the expression of the (<b>A</b>) AMPK and (<b>B</b>) mTOR genes in various groups. *** <span class="html-italic">p</span> &lt; 0.001 vs. <span class="html-italic">control</span>; <span class="html-italic"><sup>###</sup> p</span> &lt; 0.001 vs. CsA.</p> Full article ">
13 pages, 2251 KiB  
Article
Spectral Characteristics of Dissolved Organic Matter in Farmland Soils around Urumqi, China
by Jianhua Zhu, Jia Duo, Zizhao Zhang, Liang Pei, Wenfeng Li and Rehemanjiang Wufuer
Toxics 2023, 11(4), 376; https://doi.org/10.3390/toxics11040376 - 16 Apr 2023
Viewed by 1623
Abstract
The dissolved organic matter (DOM) is one of the most sensitive indicators of changes in the soil environment, and it is the most mobile and active soil component that serves as an easily available source of nutrients and energy for microbes and other [...] Read more.
The dissolved organic matter (DOM) is one of the most sensitive indicators of changes in the soil environment, and it is the most mobile and active soil component that serves as an easily available source of nutrients and energy for microbes and other living organisms. In this paper, DOM structural characteristics and main properties were investigated by three-dimensional fluorescence spectroscopy (EEM) and UV–visible spectrum technology in the farmland soils around Urumqi of China, and its possible sources and pathways were analyzed by spectroscopic indices. The results showed that humic-like substances were the main composition of the soil DOM, and its autogenesis characteristics were not obvious. Main DOM properties such as aromatability, hydrophobicity, molecular weight, molecular size, and humification degree in the southern region of Urumqi were higher than those of the northern region of Urumqi and Fukang in China, and higher on the upper layers of the soil (0–0.1 and 0.2 m) than in the deeper layer (0.2–0.3 m).This may be because the tilled layer is more subjected to fertilization and conducive to microbial activities. The spectroscopic analysis showed that the source of DOM of these regions is mainly from microbial metabolites. These results provide basic scientific data for the further research on the environmental chemical behavior of pollutants and pollution control in this region. Full article
(This article belongs to the Section Toxicity Reduction and Environmental Remediation)
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<p>The Map of the sampling points.</p> Full article ">Figure 2
<p>Typical 3D-EEM spectra of soil DOM of sample sitein S2 and S14.</p> Full article ">Figure 3
<p>Average fluorescence intensities of different soil depth on different districts.</p> Full article ">Figure 4
<p>FI (fluorescence index) and BIX (autochthonous index) of soil DOM on different districts.</p> Full article ">
16 pages, 4556 KiB  
Article
Antitumor Profile of Combined Matricaria recutita Flower Extract and 5-Fluorouracil Chemotherapy in Sarcoma 180 In Vivo Model
by Sara A. Santos, Ricardo G. Amaral, Ariel S. Graça, Silvana V. F. Gomes, Fabrício P. Santana, Iza B. de Oliveira, Luciana N. Andrade, Patrícia Severino, Ricardo L. C. de Albuquerque-Júnior, Sandra L. Santos, Eliana B. Souto and Adriana A. Carvalho
Toxics 2023, 11(4), 375; https://doi.org/10.3390/toxics11040375 - 14 Apr 2023
Cited by 2 | Viewed by 2053
Abstract
Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract [...] Read more.
Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy. Full article
(This article belongs to the Special Issue The 10th Anniversary of Toxics)
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<p>In vivo antitumor effect of 5-FU 25 mg/kg/day associated with MRFE 200 mg/kg/day in animals transplanted with sarcoma 180. The vehicle group was treated with saline and the 5-FU group with 5-Fluorouracil 25 mg/kg/day. The values correspond to the mean ± S.E.M. of 07 animals/group analyzed using one-way analysis of variance with the Student–Newman–Keuls post test. * <italic>p</italic>&lt; 0.05 compared to the vehicle group. <sup>#</sup> <italic>p</italic> &lt; 0.05 compared to the 5-FU group.</p> Full article ">Figure 2
<p>Photomicrographs of HE-stained histological sections of surgical specimens of sarcoma 180 implanted in rodents. Circles—giant tumor cells with bizarre nuclei; white arrows—typical mitotic figures; dark arrows—atypical figures; thin arrow—apoptotic bodies; dashed line—presence of tumor cell emboli within blood vessels A-C, Rx400, D-K x800, and M-Q x100. Caption: CT—viable tumor cells; NE—coagulative necrosis; TME—skeletal striated muscle tissue; TA—subcutaneous adipose tissue. (<bold>A</bold>,<bold>B</bold>) prominent nucleoli; (<bold>C</bold>) tumor giant cells with hyperchromatic misshapen nuclei; (<bold>D</bold>) prophase; (<bold>E</bold>) metaphase; (<bold>F</bold>) anaphase; (<bold>G</bold>) telophase; (<bold>H</bold>) atypical tripolar spindles; (<bold>I</bold>) atypical tetrapolar spindles; (<bold>J</bold>) atypical prophases; (<bold>K</bold>) apoptotic bodies; (<bold>M</bold>,<bold>N</bold>) comedo-type necrosis; (<bold>L</bold>) peri and intratumoral inflammatory infiltrate rich in lymphocytes; (<bold>O</bold>) tumor cells compressing the peripheral skeletal muscle tissue; (<bold>P</bold>) tumor cells invading and dissociating skeletal muscle tissue; (<bold>Q</bold>) tumor cells permeating and disorganizing the subcutaneous adipose tissue; (<bold>R</bold>) tumor cell emboli within blood vessels.</p> Full article ">Figure 3
<p>Photomicrographs of HE-stained histological sections of surgical specimens of sarcoma 180 implanted in rodents. (<bold>A</bold>) vehicle group showing tumor with infiltrative and irregular margins, invading and dissociating peripheral muscle tissue and (<bold>B</bold>) forming solid intraparenchymal blocks of coagulative necrosis. (<bold>C</bold>) 5-FU group showing regular tumor margins, with a more expansive growth pattern and (<bold>D</bold>) thin bands of coagulative necrosis forming a trabecular pattern. (<bold>E</bold>) Group treated with 100 mg/kg of the extract showing very infiltrative tumor margins and (<bold>F</bold>) forming thick intraparenchymal bands of coagulative necrosis. (<bold>G</bold>) Group treated with 200 mg/kg showing much more regular tumor margins and (<bold>H</bold>) trabeculae of intratumoral coagulative necrosis. (<bold>I</bold>,<bold>J</bold>) Group treated with 5-FU associated with 100 mg/Kg and (<bold>K</bold>,<bold>L</bold>) 200 mg/kg of the extract exhibiting regular tumor margins compressing peripheral skeletal striated muscle tissue and thin trabeculae of intratumoral coagulative necrosis. Caption: CT—viable tumor cells; NE—coagulative necrosis; TMEp—skeletal striated muscle tissue; TA—subcutaneous adipose tissue (×100).</p> Full article ">Figure 4
<p>Quantitative analysis of the mean mitosis/histological field (×400) for the different experimental groups. Data expressed as mean ± S.E.M. Data analyzed by one-way analysis of variance (ANOVA) with Tukey post test. * <italic>p</italic> &lt; 0.05 compared to the vehicle group. <sup>#</sup> <italic>p</italic> &lt; 0.05 compared to the 5-FU group.</p> Full article ">Figure 5
<p>Photomicrographs of histological sections demonstrating immunohistochemical expression of the Ki67 antigen (brownish staining) in the tumors analyzed. The tumor cells presented predominantly nuclear positivity (LSAB, 400×). (<bold>A</bold>) vehicle group; (<bold>B</bold>) 5-FU group; (<bold>C</bold>) MRFE 100 group; (<bold>D</bold>) MRFE 200 group; (<bold>E</bold>) 5-FU+MRFE 100 group; (<bold>F</bold>) 5-FU+MRFE 200 group.</p> Full article ">Figure 6
<p>Quantitative analysis of Ki67 positive cells (nuclear immunostaining) representative of the estimation of the tumor proliferative index in the different experimental groups. Significant differences from the saline group were expressed as * <italic>p</italic> &lt; 0.05, significant differences from the 5-FU group were expressed as <sup>#</sup> <italic>p</italic> &lt; 0.05 (ANOVA and Bonferroni multiple comparison post test).</p> Full article ">Figure 7
<p>Photomicrographs of HE-stained histological sections of surgical specimens of spleen from rodents with sarcoma 180. (<bold>A</bold>) Vehicle group and (<bold>B</bold>) MRFE group 200 mg/kg/day, demonstrating extensive white hair region. (<bold>C</bold>) Group 5-FU alone and (<bold>D</bold>) Group 5-FU associated with MRFE 200 mg/kg/day, showing atrophy of the white fur. (×100).</p> Full article ">
46 pages, 736 KiB  
Review
One Health Approach to Tackle Microbial Contamination on Poultries—A Systematic Review
by Bianca Gomes, Marta Dias, Renata Cervantes, Pedro Pena, Joana Santos, Marta Vasconcelos Pinto and Carla Viegas
Toxics 2023, 11(4), 374; https://doi.org/10.3390/toxics11040374 - 14 Apr 2023
Cited by 6 | Viewed by 2614
Abstract
This study reports the search of available data published regarding microbial occupational exposure assessment in poultries, following the PRISMA methodology. Air collection through filtration was the most frequently used. The most commonly used passive sampling method was material collection such as dust, cages, [...] Read more.
This study reports the search of available data published regarding microbial occupational exposure assessment in poultries, following the PRISMA methodology. Air collection through filtration was the most frequently used. The most commonly used passive sampling method was material collection such as dust, cages, soils, sediment, and wastewater. Regarding assays applied, the majority of studies comprised culture-based methods, but molecular tools were also frequently used. Screening for antimicrobial susceptibility was performed only for bacteria; cytotoxicity, virological and serological assays were also performed. Most of the selected studies focused on bacteria, although fungi, endotoxins, and β-glucans were also assessed. The only study concerning fungi and mycotoxins reported the carcinogenic mycotoxin AFB1. This study gives a comprehensive overview of microbial contamination in the poultry industry, emphasizing this setting as a potential reservoir of microbial pathogens threatening human, animal, and environmental health. Additionally, this research helps to provide a sampling and analysis protocol proposal to evaluate the microbiological contamination in these facilities. Few articles were found reporting fungal contamination in poultry farms worldwide. In addition, information concerning fungal resistance profile and mycotoxin contamination remain scarce. Overall, a One Health approach should be incorporated in exposure assessments and the knowledge gaps identified in this paper should be addressed in further research. Full article
(This article belongs to the Special Issue Risk Assessment of Occupational Exposures for Better Health)
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<p>PRISMA-based selection of articles.</p> Full article ">
15 pages, 4981 KiB  
Article
Effects of Multiwall Carbon Nanotubes on Premature Kidney Aging: Biochemical and Histological Analysis
by Ji-Eun Kim and Myung-Haing Cho
Toxics 2023, 11(4), 373; https://doi.org/10.3390/toxics11040373 - 14 Apr 2023
Cited by 1 | Viewed by 1787
Abstract
Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this [...] Read more.
Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this study, we compared the effects on the kidneys and aging for two different types of multiwall carbon nanotubes (MWCNTs): pristine MWCNTs (PMWCNTs) and acid-treated MWCNTs (TMWCNTs), with TMWCNTs being the preferred form for use as a composite material due to its superior dispersion properties. We used tracheal instillation and maximum tolerated dose (MTD) for both types of CNTs. MTD was determined as a 10% weight loss dose in a 3-month subchronic study, and the appropriate dosage for 1-year exposure was 0.1 mg/mouse. Serum and kidney samples were analyzed using ELISA, Western blot, and immunohistochemistry after 6 months and 1 year of treatment. PMWCNT-administered mice showed the activation of pathways for inflammation, apoptosis, and insufficient autophagy, as well as decreased serum Klotho levels and increased serum levels of DKK-1, FGF-23, and sclerostin, while TMWCNTs did not. Our study suggests that lung exposure to PMWCNTs can induce premature kidney aging and highlights a possible toxic effect of using MWCNTs on the kidneys in the industrial field, further highlighting that dispersibility can affect the toxicity of the nanotubes. Full article
(This article belongs to the Special Issue Nanotoxicology, Environmental Risk Assessment and Nanotoxicity Analysis of Engineered Nanomaterials (ENMs))
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<p>Characteristics of PMWCNTs and TMWCNTs. (<b>A</b>) TEM image of PMWCNTs (<b>Left</b>) and TMWCNTs (<b>Right</b>). (<b>B</b>) Raman spectra of PMWCNTs (Red) and TMWCNTs (Black). (<b>C</b>) Intensity ratio of Raman D peak and G peak. TMWCNTs show higher I<sub>D</sub>/I<sub>G</sub> ratio than that of PMWCNTs.</p> Full article ">Figure 2
<p>Schematic diagram of the animal experiment and body weight change during 3 months. (<b>A</b>) Six-week-old mice were treated with either 50 μL sterile saline, PMWCNTs, or TMWCNTs suspended in sterile saline. Five mice were included in each group, and the concentrations of PMWCNTs and TMWCNTs were either 0.01 mg/50 μL or 0.1 mg/50 μL, with each mouse receiving 50 μL of the respective treatment. The mice were dissected at 6 months and 1 year post-instillation to investigate the long-term effects of the treatments. Created with BioRender.com (<b>B</b>) Effects of MWCNTs on mouse body weight gain up until 92 days post-exposure. The average body weight of the control group was 31.7 ± 0.81 g, while the high dosage PMWCNT and TMWCNT groups had an average body weight of 29.59 ± 0.56 g and 28.89 ± 0.83 g each. The average weight of the mice at the start point was approximately 20 g. No toxicity, assessed and defined as a 10% weight loss, was observed up to 0.1 mg/mouse of TMWCNTs and PMWCNTs. Each bar represents the mean ± S.E.M. (n = 5).</p> Full article ">Figure 3
<p>Alteration of serum phosphate, blood urea nitrogen level and kidney histology by MWCNTs after 6 months of instillation. (<b>A</b>) Serum phosphate level of mice and (<b>B</b>) Serum blood urea nitrogen level of mice after treatment with saline, PMWCNTs, and TMWCNTs. (<b>C</b>) H&amp;E staining of sections of the cortex (×200) and medulla (×400) of the kidneys at 6 months post instillation of saline, PMWCNTs, and TMWCNTs. Arrows indicate increased interstitial volume in the PMWCNT-treated group. Arrow heads indicate increased glomerular size. Representative figures of five individuals from each group. Magnifications are indicated in the figures. Error bars indicate mean ± S.E.M. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.001 indicate statistical difference compared to the control group. <sup>@</sup> <span class="html-italic">p</span> &lt; 0.05 is statistical difference between 0.1 mg of PMWCNTs and TMWCNTs.</p> Full article ">Figure 4
<p>Tissue and serum Klotho level in mice after 6 months instillation. (<b>A</b>) Western blot analysis of Klotho in the kidneys of mice after 6 months of treatment with PMWCNTs and TMWCNTs. (<b>B</b>) Serum Klotho level of mice exposed to saline, 0.01 mg and 0.1 mg of PMWCNTs and TMWCNTs, respectively. * Statistically different (<span class="html-italic">p</span> &lt; 0.05) compared to the control group (n = 5). <sup>@@</sup> Statistically different (<span class="html-italic">p</span> &lt; 0.01) between the two indicated groups. <sup>##</sup> Statistical difference (<span class="html-italic">p</span> &lt; 0.01) between the two indicated groups.</p> Full article ">Figure 5
<p>Activated inflammatory, fibrotic and apoptotic pathways, and insufficient autophagy were observed in the kidneys at 6 months post tracheal instillation of PMWCNTs. (<b>A</b>) Western blot analysis of NF-κBp65, phospho-smad2, alpha-SMA, p62, F4/80 and MCP1 in the kidney of mice 6 months after the administration of PMWCNTs and TMWCNTs, and their densitometric analysis (<b>B</b>). (<b>C</b>) Western blot analysis of p53, BAX, and BAD in the kidney of mice after 6 months of treatment with PMWCNTs and TMWCNTs, and their densitometry graph (<b>D</b>) (n = 5). The bands of p53, BAX, and BAD were further analyzed using densitometry. The intensity of the p53, BAX, and BAD bands were separated by the intensity of the GAPDH band. Each bar represents the mean ± S.E.M. (n = 5). * Statistically different (<span class="html-italic">p</span> &lt; 0.05) compared to the control group (n = 5).</p> Full article ">Figure 6
<p>The effects of administering multi-walled carbon nanotubes (MWCNTs) on the morphology of mouse kidneys after one year. (<b>A</b>) Hematoxylin and eosin-stained images show the morphologies of mouse kidneys treated with saline, PMWCNTs, and TMWCNTs. (<b>B</b>) PMWCNTs induce hydronephrosis after one year. Inset shows traces of the glomerulus. (<b>C</b>) Paraffin-embedded kidney tissue sections one year after the administration of PMWCNTs and TMWCNTs were stained with H&amp;E and Masson’s trichrome. Red arrow indicates tubular epithelial vacuolation. Empty arrow indicates tubular epithelial necrosis. Arrow head indicates tubular dilation. Empty arrow head indicates lymphocyte infiltration. Dashed arrow and dashed empty arrow indicate tubulointerstitial fibrosis and glomerulosclerosis, respectively. Magnification and scale bar are indicated in each figure.</p> Full article ">Figure 7
<p>Serum analysis of mice after 1 year of instillation. (<b>A</b>) Serum phosphate, (<b>B</b>) Blood urea nitrogen, (<b>C</b>) Serum Klotho, (<b>D</b>) Serum DKK-1, (<b>E</b>) Serum FGF-23 and (<b>F</b>) Serum sclerostin levels after 1 year of treatment with saline, PMWCNTs, and TMWCNTs. Each bar represents the mean ± S.E.M. (n = 5). * Statistically different (<span class="html-italic">p</span> &lt; 0.05) compared to the control group. ** Statistically different (<span class="html-italic">p</span> &lt; 0.01) compared to the control group. <sup>#</sup> Statistical difference (<span class="html-italic">p</span> &lt; 0.05) between the two indicated groups. <sup>###</sup> Statistically different (<span class="html-italic">p</span> &lt; 0.001) between the two indicated groups.</p> Full article ">
10 pages, 263 KiB  
Article
Human Poisoning with Methomyl and Cypermethrin Pesticide Mixture
by Chi-Ang Liang, Shu-Sen Chang, Hsien-Yi Chen, Kai-Fan Tsai, Wen-Chin Lee, I-Kuan Wang, Chao-Yu Chen, Shou-Hsuan Liu, Cheng-Hao Weng, Wen-Hung Huang, Ching-Wei Hsu and Tzung-Hai Yen
Toxics 2023, 11(4), 372; https://doi.org/10.3390/toxics11040372 - 14 Apr 2023
Cited by 4 | Viewed by 3193
Abstract
There is limited literature analyzing the outcome of human poisoning with methomyl and cypermethrin pesticide mixture. Between 2002 and 2018, a total of 63 patients intoxicated with methomyl, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. The patients were [...] Read more.
There is limited literature analyzing the outcome of human poisoning with methomyl and cypermethrin pesticide mixture. Between 2002 and 2018, a total of 63 patients intoxicated with methomyl, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. The patients were categorized into three groups based on the type of pesticide, as methomyl (n = 10), cypermethrin (n = 31), or methomyl and cypermethrin (n = 22). Demographic, clinical, laboratory, and mortality data were obtained for analysis. The patients were aged 54.9 ± 18.9 years. Following ingestion, the patients experienced a wide range of clinical symptoms, including aspiration pneumonia (50.8%), acute respiratory failure (41.3%), acute kidney injury (33.3%), multiple organ failure (19.0%), emesis (19.0%), acute hepatitis (12.7%), diarrhea (7.9%), seizures (4.8%), lacrimation (4.8%), etc. After analysis, it was found that patients with methomyl and cypermethrin poisoning suffered higher incidences of acute respiratory failure (p < 0.001), aspiration pneumonia (p = 0.004), acute kidney injury (p = 0.011), and multiple organ failure (p < 0.001) than the other groups. Laboratory analyses revealed that patients with methomyl and cypermethrin poisoning had a higher creatinine level (p = 0.011), white blood cell count (p < 0.001), and neutrophil count (p = 0.019) than the other groups. A total of seven (11.1%) patients died. The average duration of hospitalization was 9.8 ± 10.0 days. In a multivariate logistic regression model, it was revealed that methomyl pesticide (p = 0.045) or methomyl and cypermethrin pesticide mixture (p = 0.013) were significant risk factors for acute respiratory failure. Nevertheless, no mortality risk factor could be identified. Therefore, the analytical results suggest that methomyl pesticide is the major contributor to the toxicity of methomyl and cypermethrin pesticide mixture poisoning. More research is needed. Full article
(This article belongs to the Special Issue Hazardous Effects of Pesticides on Human Health)
20 pages, 3434 KiB  
Article
The Difference between Rhizosphere and Endophytic Bacteria on the Safe Cultivation of Lettuce in Cr-Contaminated Farmland
by Zheyu Wen, Qizhen Liu, Chao Yu, Lukuan Huang, Yaru Liu, Shun’an Xu, Zhesi Li, Chanjuan Liu and Ying Feng
Toxics 2023, 11(4), 371; https://doi.org/10.3390/toxics11040371 - 13 Apr 2023
Cited by 7 | Viewed by 2515
Abstract
Chromium (Cr) is a major pollutant affecting the environment and human health and microbial remediation is considered to be the most promising technology for the restoration of the heavily metal-polluted soil. However, the difference between rhizosphere and endophytic bacteria on the potential of [...] Read more.
Chromium (Cr) is a major pollutant affecting the environment and human health and microbial remediation is considered to be the most promising technology for the restoration of the heavily metal-polluted soil. However, the difference between rhizosphere and endophytic bacteria on the potential of crop safety production in Cr-contaminated farmland is not clearly elucidated. Therefore, eight Cr-tolerant endophytic strains of three species: Serratia (SR-1~2), Lysinebacillus (LB-1~5) and Pseudomonas (PA-1) were isolated from rice and maize. Additionally, one Cr-tolerant strain of Alcaligenes faecalis (AF-1) was isolated from the rhizosphere of maize. A randomized group pot experiment with heavily Cr-contaminated (a total Cr concentration of 1020.18 mg kg−1) paddy clay soil was conducted and the effects of different bacteria on plant growth, absorption and accumulation of Cr in lettuce (Lactuca sativa var. Hort) were compared. The results show that: (i) the addition of SR-2, PA-1 and LB-5 could promote the accumulation of plant fresh weight by 10.3%, 13.5% and 14.2%, respectively; (ii) most of the bacteria could significantly increase the activities of rhizosphere soil catalase and sucrase, among which LB-1 promotes catalase activity by 224.60% and PA-1 increases sucrase activity by 247%; (iii) AF-1, SR-1, LB-1, SR-2, LB-2, LB-3, LB-4 and LB-5 strains could significantly decrease shoot the Cr concentration by 19.2–83.6%. The results reveal that Cr-tolerant bacteria have good potential to reduce shoot Cr concentration at the heavily contaminated soil and endophytic bacteria have the same or even better effects than rhizosphere bacteria; this suggests that bacteria in plants are more ecological friendly than bacteria in soil, thus aiming to safely produce crops in Cr-polluted farmland and alleviate Cr contamination from the food chain. Full article
(This article belongs to the Section Toxicity Reduction and Environmental Remediation)
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<p>S-CAT and S-SC activity in the rhizosphere soil of different treatments. (<b>A</b>): S-CAT activity in soil. (<b>B</b>) S-SC activity in soil. The same letter means no significant difference.</p> Full article ">Figure 2
<p>Total Cr and Cr (VI) concentration in the rhizosphere soil of different treatments. (<b>A</b>): Total Cr concentration in soil; (<b>B</b>): Cr (VI) concentration in soil. The same letter means no significant difference.</p> Full article ">Figure 3
<p>The growth of lettuce in different treatments.</p> Full article ">Figure 4
<p>The Cr uptake, translocation and bioaccumulation of plants in different treatments. The data are average of three replicates ± SE. (<b>A</b>): Cr concentration in shoot; (<b>B</b>): Cr accumulation in shoot; (<b>C</b>): Translocation factor; (<b>D</b>): Bioaccumulation factor. The same letter means no significant difference.</p> Full article ">Figure 5
<p>Correlation analysis of basic physicochemical properties, enzyme activities, Cr bioavailability in rhizosphere soil and Cr bioaccumulation in plant. Cr: soil total Cr content, Cr (VI): soil Cr (VI) content, F.W.: fresh weight, Ca: chlorophyll a, Cb: chlorophyll b, Ctotal: total chlorophyll, Cr-A: Cr accumulation in shoot, Cr-C: Cr concentration in shoot.</p> Full article ">
13 pages, 4050 KiB  
Article
Acute Toxicity of the Dinoflagellate Amphidinium carterae on Early Life Stages of Zebrafish (Danio rerio)
by Xiao Yang, Zhi Yan, Jingjing Chen, Derui Wang and Ke Li
Toxics 2023, 11(4), 370; https://doi.org/10.3390/toxics11040370 - 13 Apr 2023
Cited by 6 | Viewed by 2169
Abstract
Dinoflagellates of the genus Amphidinium can produce a variety of polyketides, such as amphidinols (AMs), amphidinoketides, and amphidinin, that have hemolytic, cytotoxic, and fish mortality properties. AMs pose a significant threat to ecological function due to their membrane-disrupting and permeabilizing properties, as well [...] Read more.
Dinoflagellates of the genus Amphidinium can produce a variety of polyketides, such as amphidinols (AMs), amphidinoketides, and amphidinin, that have hemolytic, cytotoxic, and fish mortality properties. AMs pose a significant threat to ecological function due to their membrane-disrupting and permeabilizing properties, as well as their hydrophobicity. Our research aims to investigate the disparate distribution of AMs between intracellular and extracellular environments, as well as the threat that AMs pose to aquatic organisms. As a result, AMs containing sulphate groups such as AM19 with lower bioactivity comprised the majority of A. carterae strain GY-H35, while AMs without sulphate groups such as AM18 with higher bioactivity displayed a higher proportion and hemolytic activity in the extracellular environment, suggesting that AMs may serve as allelochemicals. When the concentration of extracellular crude extracts of AMs reached 0.81 µg/mL in the solution, significant differences in zebrafish embryonic mortality and malformation were observed. Over 96 hpf, 0.25 μL/mL of AMs could cause significant pericardial edema, heart rate decrease, pectoral fin deformation, and spinal deformation in zebrafish larvae. Our findings emphasized the necessity of conducting systematic research on the differences between the intracellular and extracellular distribution of toxins to gain a more accurate understanding of their effects on humans and the environment. Full article
(This article belongs to the Section Ecotoxicology)
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<p>Chemical structures of amphidinol 3 (AM3, <b>A</b>) and amphidinol 25 (AM25, <b>B</b>).</p> Full article ">Figure 2
<p>Main MS/MS fragments observed for amphidinol 18 (<b>A</b>), amphidinol 19 (<b>B</b>), and amphidinol 2 (<b>C</b>).</p> Full article ">Figure 3
<p>The hatching rate of zebrafish embryos exposed to AMs for each observation time. Hatching rate was calculated with the equation (number of hatched individuals)/(survival individuals of one replicate) and represented as the mean ± SD (n = 3). Tukey’s multiple comparison test and one-way ANOVA were used to examine the results of the experiments. NS was regarded as having no significant difference.</p> Full article ">Figure 4
<p>Morphological abnormalities induced by AMs from <span class="html-italic">A. carterae</span> at different times. The normal zebrafish embryos in the control group were at 24 hpf (<b>A-1</b>), 48 hpf (<b>A-2</b>), and 72 hpf (<b>A-3</b>). Typical malformations caused by 2.03 µg/mL of AMs on zebrafish embryonic development at 24 hpf (<b>B-1</b>), 48 hpf (<b>B-2</b>), and 72 hpf (<b>B-3</b>). Abbreviations: Pe, pericardial edema; Pfd, pectoral fin deformities; Sd, spinal deformation; Td, tail extension deformity; Ye, yolk edema; Ysd, yolk sac deformity.</p> Full article ">Figure 5
<p>(<b>A</b>) Malformation rate at 72 hpf; (<b>B</b>) number of spontaneous movements per minute at 24 hpf; (<b>C</b>) body length of hatched individual at 96 hpf; (<b>D</b>) heart rate per minute at 96 hpf; (<b>E</b>) pericardium area at 96 hpf. Values represented averages from four replicates with standard deviation as error bars. An asterisk indicates a significant difference between the treatment and the control (one-way ANOVA, Turkey’s HSD at <span class="html-italic">p</span> &lt; 0.05 denoted by *, <span class="html-italic">p</span> &lt; 0.01 denoted by **).</p> Full article ">
16 pages, 3310 KiB  
Article
The Adsorption Behaviors and Mechanisms of Humic Substances by Thermally Oxidized Graphitic Carbon Nitride
by Hongxin Li, Jianlong Wang, Dongbei Yue, Jianchao Wang, Chu Tang and Lingyue Zhang
Toxics 2023, 11(4), 369; https://doi.org/10.3390/toxics11040369 - 12 Apr 2023
Cited by 4 | Viewed by 1790
Abstract
Thermal oxidation is efficient for enhancing the photocatalysis performance of graphitic carbon nitride (g-C3N4), while its effect on adsorption performance has not been fully studied, which is crucial to the application of g-C3N4 as adsorbents and [...] Read more.
Thermal oxidation is efficient for enhancing the photocatalysis performance of graphitic carbon nitride (g-C3N4), while its effect on adsorption performance has not been fully studied, which is crucial to the application of g-C3N4 as adsorbents and photocatalysts. In this study, thermal oxidation was used to prepare sheet-like g-C3N4 (TCN), and its application for adsorption of humic acids (HA) and fulvic acids (FA) was evaluated. The results showed that thermal oxidation clearly affected the properties of TCN. After thermal oxidation, the adsorption performance of TCN was enhanced significantly, and the adsorption amount of HA increased from 63.23 (the bulk g-C3N4) to 145.35 mg/g [TCN prepared at 600 °C (TCN-600)]. Based on fitting results using the Sips model, the maximum adsorption amounts of TCN-600 for HA and FA were 327.88 and 213.58 mg/g, respectively. The adsorption for HA and FA was markedly affected by pH, alkaline, and alkaline earth metals due to electrostatic interactions. The major adsorption mechanisms included electrostatic interactions, π-π interactions, hydrogen bonding, along with a special pH-dependent conformation (for HA). These findings implied that TCN prepared from environmental-friendly thermal oxidation showed promising prospects for humic substances (HSs) adsorption in natural water and wastewater. Full article
(This article belongs to the Special Issue Toxicity Characterization, Detection and Remediation of Contaminants in Soils and Groundwater)
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Full article ">Figure 1
<p>(<b>a</b>) The XRD patterns, (<b>b</b>) FT-IR spectra, (<b>c</b>) N 1s core region, (<b>d</b>) C 1s core region, and (<b>e</b>) SEM images of the bulk g-C<sub>3</sub>N<sub>4</sub> and TCN samples.</p> Full article ">Figure 2
<p>(<b>a</b>) The nitrogen adsorption–desorption isotherms, (<b>b</b>) pore-size distribution, (<b>c</b>) surface areas, and (<b>d</b>) pore volume of the bulk g-C<sub>3</sub>N<sub>4</sub> and TCN.</p> Full article ">Figure 3
<p>(<b>a</b>–<b>c</b>) The adsorption kinetics of HA on TCN (C<sub>HSs</sub> = 100 mg/L, pH = 3.0, T = 298.5 K, C<sub>TCN</sub> = 0.4 g/L, and I = 0.01 M); (<b>d</b>) The adsorption kinetics of FA on TCN-600 (C<sub>HSs</sub> = 50 mg/L, pH = 3.0, T = 298.5 K, C<sub>TCN-600</sub> = 0.4 g/L, and I = 0.01 M); (<b>e</b>,<b>f</b>) The intraparticle diffusion of HA and FA on TCN-600 [C<sub>HSs</sub> = 100 (HA) or 50 (FA) mg/L, pH = 3.0, T = 298.5 K, C<sub>TCN-600</sub> = 0.4 g/L, and I = 0.01 M].</p> Full article ">Figure 4
<p>The effects of (<b>a</b>,<b>c</b>) alkali metals and (<b>b</b>,<b>d</b>) alkali earth metals [C<sub>HSs</sub> = 50 mg/L, pH = 3.0, T = 298.5 K, C<sub>TCN-600</sub> = 0.4 g/L, I = 0.01 M (for K<sup>+</sup>, Ca<sup>2+</sup>, and Mg<sup>2+</sup>)] on the adsorption of HA and FA to TCN-600.</p> Full article ">Figure 5
<p>The adsorption isotherms of (<b>a</b>–<b>d</b>) HA and (<b>e</b>–<b>h</b>) FA to TCN-600 (C<sub>HSs</sub> = 25–200 mg/L, pH = 3.0, C<sub>TCN-600</sub> = 0.4 g/L, and I = 0.01 M, T = 298.5, 308.5, and 318.5 K).</p> Full article ">Figure 6
<p>(<b>a</b>) The nitrogen adsorption–desorption isotherms, (<b>b</b>) specific surface area, (<b>c</b>) pore volume, (<b>d</b>) XPS spectra, (<b>e</b>) N 1s core region, and (<b>f</b>) C 1s core region before and after adsorption of HA and FA (C<sub>HSs</sub> = 50 mg/L, pH = 3.0, C<sub>TCN-600</sub> = 0.4 g/L t = 120 min, and I = 0.01 M).</p> Full article ">Figure 7
<p>The EEM of HA and FA before (<b>a</b>,<b>c</b>) and after (<b>b</b>,<b>d</b>) adsorption by TCN-600 (C<sub>HSs</sub> = 50 mg/L, pH = 3.0, t = 120 min, and I = 0.01 M).</p> Full article ">
15 pages, 2638 KiB  
Article
The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
by Alaa M. Hammad, Baraa Shawaqfeh, Suhair Hikmat, Tariq Al-Qirim, Lama Hamadneh, Sameer Al-Kouz, Mariam M. Awad and Frank S. Hall
Toxics 2023, 11(4), 368; https://doi.org/10.3390/toxics11040368 - 12 Apr 2023
Cited by 2 | Viewed by 2306
Abstract
Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and [...] Read more.
Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and olfactory bulb) was examined. Twenty pregnant female Wistar rats at gestational day 18 were used. Pregnant rats were divided into four groups: Control, APAP, E + APAP, and APAP + E. The Control group was treated with 0.5 mL p.o. corn oil. The APAP group received 3000 mg/kg p.o. APAP. The E + APAP group received 300 mg/kg p.o. vitamin E one hour before 3000 mg/kg APAP. The APAP + E group received 3000 mg/kg paracetamol one hour before 300 mg/kg p.o. vitamin E. Twenty-four hours after the last treatment administration, rats were euthanized and blood, brain, liver, and kidney samples were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine levels, uric acid (UA), and superoxide dismutase (SOD) levels, as well as the relative mRNA expression of Cyp1a4, Cyp2d6, and Nat2, were determined. Acute APAP treatment upregulated ALT, AST, BUN, and creatinine levels. APAP treatment downregulated UA and SOD levels. APAP treatment upregulated the relative mRNA expression of Cyp1a4 and Cyp2d6, but downregulated Nat2 expression. Vitamin E treatment, either before or after APAP administration, attenuated the toxic effects of APAP. In conclusion, the results showed that an acute toxic APAP dose in late pregnancy can cause oxidative stress and dysregulation in Cyp isoform expression, and that vitamin E treatment attenuates these effects. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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<p>Blood biochemistry showing hepatotoxicity and nephrotoxicity after a single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (means ± SEM): (<b>A</b>) ALT levels, (<b>B</b>) AST levels, (<b>C</b>) SCr levels, and (<b>D</b>) BUN levels (****: <span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">Figure 2
<p>UA levels in different organs and brain regions after a single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (means ± SEM): (<b>A</b>) liver, (<b>B</b>) kidney, (<b>C</b>) hippocampus, (<b>D</b>) cerebellum, and (<b>E</b>) olfactory bulbs (*: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01, ***: <span class="html-italic">p</span> &lt; 0.001, ****: <span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">Figure 3
<p>SOD inhibition (%) in different organs and brain regions after a single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (mean ± SEM): (<b>A</b>) liver, (<b>B</b>) kidney, (<b>C</b>) hippocampus, (<b>D</b>) cerebellum, and (<b>E</b>) olfactory bulbs (****: <span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">Figure 4
<p>Relative <span class="html-italic">Cyp1a4</span> mRNA expression in different organs and brain regions after single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (mean ± SEM): (<b>A</b>) liver, (<b>B</b>) kidney, (<b>C</b>) hippocampus, and (<b>D</b>) cerebellum (*: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01, ****: <span class="html-italic">p</span> &lt; 0.0001, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">Figure 5
<p>Relative <span class="html-italic">Cyp2d6</span> mRNA expression in different organs and brain regions after single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (mean ± SEM): (<b>A</b>) liver, (<b>B</b>) kidney, (<b>C</b>) hippocampus, and (<b>D</b>) cerebellum (*: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">Figure 6
<p>Relative <span class="html-italic">Nat2</span> mRNA expression in different organs and brain regions after a single acute APAP (3000 mg/kg) administration and vitamin E (300 mg/kg) treatment (mean ± SEM): (<b>A</b>) liver, (<b>B</b>) kidney, (<b>C</b>) hippocampus, and (<b>D</b>) cerebellum (*: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01, ***: <span class="html-italic">p</span> &lt; 0.001, <span class="html-italic">n</span> = 5 for each group). Individual data points are shown in the figure.</p> Full article ">
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