Antioxidants

24 pages, 6300 KiB

Open AccessArticle

Nrf2 as a Therapeutic Target in the Resistance to Targeted Therapies in Melanoma

by Marie Angèle Cucci, Margherita Grattarola, Chiara Monge, Antonella Roetto, Giuseppina Barrera, Emilia Caputo, Chiara Dianzani and Stefania Pizzimenti

Antioxidants 2023, 12(6), 1313; https://doi.org/10.3390/antiox12061313 - 20 Jun 2023

Cited by 2 | Viewed by 3299

Abstract

The use of specific inhibitors towards mutant BRAF (BRAFi) and MEK (MEKi) in BRAF-mutated patients has significantly improved progression-free and overall survival of metastatic melanoma patients. Nevertheless, half of the patients still develop resistance within the first year of therapy. Therefore, understanding the [...] Read more.

The use of specific inhibitors towards mutant BRAF (BRAFi) and MEK (MEKi) in BRAF-mutated patients has significantly improved progression-free and overall survival of metastatic melanoma patients. Nevertheless, half of the patients still develop resistance within the first year of therapy. Therefore, understanding the mechanisms of BRAFi/MEKi-acquired resistance has become a priority for researchers. Among others, oxidative stress-related mechanisms have emerged as a major force. The aim of this study was to evaluate the contribution of Nrf2, the master regulator of the cytoprotective and antioxidant response, in the BRAFi/MEKi acquired resistance of melanoma. Moreover, we investigated the mechanisms of its activity regulation and the possible cooperation with the oncogene YAP, which is also involved in chemoresistance. Taking advantage of established in vitro melanoma models resistant to BRAFi, MEKi, or dual resistance to BRAFi/MEKi, we demonstrated that Nrf2 was upregulated in melanoma cells resistant to targeted therapy at the post-translational level and that the deubiquitinase DUB3 participated in the control of the Nrf2 protein stability. Furthermore, we found that Nrf2 controlled the expression of YAP. Importantly, the inhibition of Nrf2, directly or through inhibition of DUB3, reverted the resistance to targeted therapies. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease)

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16 pages, 1700 KiB

Open AccessArticle

Impact of Modern Oven Treatments on Lipid Oxidation and Vitamin E Content of Fillets from Sardine (Sardina pilchardus) at Different Reproductive Cycle Phases

by Ancuta Nartea, Lama Ismaiel, Emanuela Frapiccini, Pasquale Massimiliano Falcone, Deborah Pacetti, Natale Giuseppe Frega, Paolo Lucci and Sabrina Colella

Antioxidants 2023, 12(6), 1312; https://doi.org/10.3390/antiox12061312 - 20 Jun 2023

Viewed by 1742

Abstract

The beneficial effects of sardine consumption can be related to the presence of bioactive compounds, such as vitamin E and ω3 polyunsaturated fatty acids. In any case, the levels of these compounds in sardine fillet depend on different factors mainly related to the [...] Read more.

The beneficial effects of sardine consumption can be related to the presence of bioactive compounds, such as vitamin E and ω3 polyunsaturated fatty acids. In any case, the levels of these compounds in sardine fillet depend on different factors mainly related to the diet and reproductive cycle phase of the fish as well as the technological treatments carried out to cook the fillets. The aim of the present study is two-fold: first, to evaluate changes in the total fatty acid profile, lipid oxidation, and vitamin E content of raw fillets from sardine (Sardina pilchardus) at different reproductive cycle phases (pre-spawning, spawning, and post-spawning); and second, to highlight how these nutritional profiles are affected by three oven treatments (conventional, steam, and sous-vide). For this purpose, raw fish was grouped into pre-spawning, spawning, and post-spawning phases according to the mesenteric fat frequency and the gonadosomatic index evaluation, and submitted to conventional (CO), steam (SO), and sous-vide (SV) baking. The ratio of EPA/DHA and vitamin E increased from post-spawning to pre-spawning, to spawning. Considering the reproductive phases, baking affected the oxidative degree differently: a CO > SO ≥ SV impact was found in the worst scenario (post-spawning), mitigated by vitamin E, to CO ≥ SO > SV in the best scenario (spawning). SV was the best treatment with high values of vitamin E in pre-spawning individuals (110.1 mg/kg). This study shows how vitamin E is correlated to the combined effect of endogenous and exogenous factors. Full article

(This article belongs to the Special Issue Impact of Processing on Antioxidant Rich Foods - 2nd Edition)

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Evolution of SFA, MUFA, ω6 PUFA, EPA, and DHA contents (weight % of total fatty acids), and ω3/ω6 PUFA ratio during the reproductive cycle is reported as three phases: pre-spawning, spawning, and post-spawning. Data are expressed as mean value ± standard deviation (n = 3). Different letters per variable mean statistical difference (p < 0.01). Full article ">Figure 2
Evolution of PV, TBARS, and vitamin E during the reproductive cycle is reported as three phases: pre-spawning, spawning, and post-spawning. Data are expressed as mean value ± standard deviation. Different letters per variable means statistical difference (p < 0.01). PV = meqO2/kg oil; TBARS = µmol/g oil; vitamin E = mg/kg oil. Full article ">Figure 3
Partial least squares-discriminant analysis (PLS-DA) of fatty acid composition (weight % of total fatty acids) based on (a) reproductive cycle stage (pre-spawning, Pre-Sp; spawning; and post-spawning, Post-SP) and on (b) oven treatment (CO, SO, and SV). CO = conventional oven; SO = steam oven; SV = sous-vide oven. Full article ">Figure 4
Evolution of (a) vitamin E (mg/kg oil), (b) PV (meqO2/kg oil), and (c) TBARS (µmol/g oil), in pre-spawning, spawning, and post-spawning sardines, raw and baked with different techniques: conventional oven (CO), steam oven (SO), and sous-vide (SV) oven. Values are means of three replicates ± standard deviation. Bars having different lowercase letters are significantly different at p < 0.05 within the same reproductive phase. Full article ">Figure 5
Box plots of normalized concentrations of PV and vitamin E of baked (CO, SO, and SV) fillets in prespawning (Pre Sp), spawning, and post-spawning (Post Sp) groups (a). CO = conventional oven; SO = steam oven; SV = sous-vide oven. Pearson’s correlation of vitamin E/PV, vitamin E/TBARs of all raw and baked samples (b). Full article ">

18 pages, 5859 KiB

Open AccessArticle

Whey Improves In Vitro Endothelial Mitochondrial Function and Metabolic Redox Status in Diabetic State

by Elisa Martino, Amalia Luce, Anna Balestrieri, Luigi Mele, Camilla Anastasio, Nunzia D’Onofrio, Maria Luisa Balestrieri and Giuseppe Campanile

Antioxidants 2023, 12(6), 1311; https://doi.org/10.3390/antiox12061311 - 20 Jun 2023

Cited by 4 | Viewed by 1670

Abstract

Endothelial dysfunction plays a critical role in the progression of type 2 diabetes mellitus (T2DM), leading to cardiovascular complications. Current preventive antioxidant strategies to reduce oxidative stress and improve mitochondrial function in T2DM highlight dietary interventions as a promising approach, stimulating the deepening [...] Read more.

Endothelial dysfunction plays a critical role in the progression of type 2 diabetes mellitus (T2DM), leading to cardiovascular complications. Current preventive antioxidant strategies to reduce oxidative stress and improve mitochondrial function in T2DM highlight dietary interventions as a promising approach, stimulating the deepening of knowledge of food sources rich in bioactive components. Whey (WH), a dairy by-product with a considerable content of bioactive compounds (betaines and acylcarnitines), modulates cancer cell metabolism by acting on mitochondrial energy metabolism. Here, we aimed at covering the lack of knowledge on the possible effect of WH on the mitochondrial function in T2DM. The results showed that WH improved human endothelial cell (TeloHAEC) function during the in vitro diabetic condition mimicked by treating cells with palmitic acid (PA) (0.1 mM) and high glucose (HG) (30 mM). Of note, WH protected endothelial cells from PA+HG-induced cytotoxicity (p < 0.01) and prevented cell cycle arrest, apoptotic cell death, redox imbalance, and metabolic alteration (p < 0.01). Moreover, WH counteracted mitochondrial injury and restored SIRT3 levels (p < 0.01). The SiRNA-mediated suppression of SIRT3 abolished the protective effects exerted by WH on the mitochondrial and metabolic impairment caused by PA+HG. These in vitro results reveal the efficacy of whey as a redox and metabolic modulator in the diabetic state and pave the way for future studies to consider whey as the source of dietary bioactive molecules with health benefits in preventive strategies against chronic diseases. Full article

(This article belongs to the Special Issue Mitochondrial Management of ROS in Physiological and Pathological Conditions)

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Whey effects on PA+HG-perturbated cell cycle. EC viability following exposure for different times and doses to (A) glucose (HG), (B) palmitic acid (PA), and (C) whey (WH). (D) Viability and (E) cytotoxicity evaluated on EC after 48 h exposure to PA+HG (0.1 mM and 30 mM, respectively) with or without WH supplementation (20% v/v). (F,G) Representative cell cycle detection by cytometric analysis and immunoblotting analysis with cropped blots of (H) cyclin D1 and (I) cyclin E1. Data are reported as mean ± SD of n = 3 independent experiments. M = molecular weight markers, lane 1 = Ctr, lane 2 = WH, Lane 3 = PA+HG, lane 4 = WH+PA+HG. Western blotting results are expressed as arbitrary units (AU). * p < 0.05 vs. 0 or Ctr; † p < 0.01 vs. 0 or Ctr; ‡ p < 0.001 vs. 0 or Ctr; • p < 0.05 vs. PA+HG; § p < 0.01 vs. PA+HG. Full article ">Figure 2
Whey reduced the PA+HG-mediated apoptosis. (A,B) Representative FACS analysis of annexin V-FITC and PI-staining and immunoblotting analysis with cropped blots of (C) procaspase-9, (D) caspase-3, (E) PARP, (F) Bax, (G) Bcl-2, and (H) Bax/Bcl-2 ratio. Q1: necrotic cells; Q2: late apoptotic cells; Q3: early apoptotic cells; Q4: viable cells. Data are reported as mean ± SD of n = 3 independent experiments. M = molecular weight markers, lane 1 = Ctr, lane 2 = WH, Lane 3 = PA+HG, lane 4 = WH+PA+HG. Western blotting results are expressed as arbitrary units (AU). * p < 0.05 vs. Ctr; † p < 0.01 vs. Ctr; ‡ p < 0.001 vs. Ctr; • p < 0.05 vs. PA+HG; § p < 0.01 vs. PA+HG. Full article ">Figure 3
Whey prevented the PA+HG-related ROS accrual. (A) MDA content, (B) extracellular ROS levels and representative fluorescent images and FACS analysis of (C,D) intracellular and (E,F) mitochondrial ROS. Scale bars = 100 μm. (G) Immunoblotting analysis with cropped blots of COX-IV protein levels. Data are reported as mean ± SD of n = 3 independent experiments. M = molecular weight markers, lane 1 = Ctr, lane 2 = WH, Lane 3 = PA+HG, lane 4 = WH+PA+HG. Western blotting results are expressed as arbitrary units (AU). † p < 0.01 vs. Ctr; ‡ p < 0.001 vs. Ctr; • p < 0.05 vs. PA+HG; § p < 0.01 vs. PA+HG. Full article ">Figure 4
Whey ameliorated the PA+HG-induced mitochondrial damage. (A–C) Representative fluorescent images and FACS analysis of mitochondrial membrane potential and (D) HDAC3 activity. SIRT3 levels evaluated by (E) ELISA kit and (F) immunoblotting analysis. Scale bars = 100 μm. Data are reported as mean ± SD of n = 3 independent experiments. M = molecular weight markers, lane 1 = Ctr, lane 2 = WH, Lane 3 = PA+HG, lane 4 = WH+PA+HG. Western blotting results are expressed as arbitrary units (AU). * p < 0.05 vs. Ctr; † p < 0.01 vs. Ctr; ‡ p < 0.001 vs. Ctr; • p < 0.05 vs. PA+HG. Full article ">Figure 5
Whey beneficial effects on mitochondrial and metabolic homeostasis. (A) ATP production coupled respiration, (B) maximal and (C) basal respiration, and (D) coupling efficiency assessed by Seahorse analyzer. (E) NAD+/NADH and (F) GSH/GSSG ratios, (G) ATP levels, (H) lactate content and immunoblotting analysis with cropped blots of (I) LDH, (J) PPAR-α, (K) PPAR-γ, and (L) SREBP1. Data are reported as mean ± SD of n = 3 independent experiments. M = molecular weight markers, lane 1 = Ctr, lane 2 = WH, Lane 3 = PA+HG, lane 4 = WH+PA+HG. Western blotting results are expressed as arbitrary units (AU). * p < 0.05 vs. Ctr; † p < 0.01 vs. Ctr; ‡ p < 0.001 vs. Ctr; • p < 0.05 vs. PA+HG; § p < 0.01 vs. PA+HG. Full article ">Figure 6
SIRT3 depletion abolished the protective effects of whey. (A) Representative immunoblotting analysis with cropped blot of SIRT3 protein levels in EC treated with empty transfection reagent (Vehicle) or transfected with nontargeting siRNA control (NT) or SIRT3 siRNA (SIRT3−). M = weight markers, lane 1 = Ctr, lane 2 = Vehicle, lane 3 = NT, lane 4 = SIRT3-. Western blotting data are expressed as arbitrary units (AU). (B–D) Representative fluorescent images and FACS analysis of mitochondrial membrane potential. Scale bars = 100 μm. Data are reported as mean ± SD of n = 3 independent experiments. ‡ p < 0.001 vs. NT; • p < 0.05 vs. NT+PA+HG. Full article ">Figure 7
SIRT3 silencing suppressed the whey beneficial effects on metabolic pathways. (A–C) Representative fluorescent images and FACS analysis of mitochondrial ROS. Scale bars = 100 μm. Detection of (D) NAD+/NADH and (E) GSH/GSSG ratios, (F) ATP levels, and (G) lactate content. Data are reported as mean ± SD of n = 3 independent experiments. * p < 0.05 vs. NT; † p < 0.01 vs. NT; ‡ p < 0.001 vs. NT; • p < 0.05 vs. NT+PA+HG; § p < 0.01 vs. NT+PA+HG. Full article ">

23 pages, 2542 KiB

Open AccessArticle

Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles

by Ana Belén Uceda, Juan Frau, Bartolomé Vilanova and Miquel Adrover

Antioxidants 2023, 12(6), 1310; https://doi.org/10.3390/antiox12061310 - 20 Jun 2023

Cited by 1 | Viewed by 1322

Abstract

Parkinson’s disease (PD) is characterized by dopaminergic neuron degeneration and the accumulation of neuronal inclusions known as Lewy bodies, which are formed by aggregated and post-translationally modified α-synuclein (αS). Oxidative modifications such as the formation of 3-nitrotyrosine (3-NT) or di-tyrosine are found in [...] Read more.

Parkinson’s disease (PD) is characterized by dopaminergic neuron degeneration and the accumulation of neuronal inclusions known as Lewy bodies, which are formed by aggregated and post-translationally modified α-synuclein (αS). Oxidative modifications such as the formation of 3-nitrotyrosine (3-NT) or di-tyrosine are found in αS deposits, and they could be promoted by the oxidative stress typical of PD brains. Many studies have tried to elucidate the molecular mechanism correlating nitroxidation, αS aggregation, and PD. However, it is unclear how nitroxidation affects the physiological function of αS. To clarify this matter, we synthetized an αS with its Tyr residues replaced by 3-NT. Its study revealed that Tyr nitroxidation had no effect on either the affinity of αS towards anionic micelles nor the overall structure of the micelle-bound αS, which retained its α-helical folding. Nevertheless, we observed that nitroxidation of Y39 lengthened the disordered stretch bridging the two consecutive α-helices. Conversely, the affinity of αS towards synaptic-like vesicles diminished as a result of Tyr nitroxidation. Additionally, we also proved that nitroxidation precluded αS from performing its physiological function as a catalyst of the clustering and the fusion of synaptic vesicles. Our findings represent a step forward towards the completion of the puzzle that must explain the molecular mechanism behind the link between αS-nitroxidation and PD. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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Features of αS primary sequence and of its nitroxidation pathways in vivo. (A) Primary sequence of αS in which the Tyr residues are circled to highlight them and the regions corresponding to the distinct domains are in squares in different colors (i.e., the N-terminal domain in purple; the NAC domain in green; the C-terminal domain in orange). (B) Scheme of the free radical pathways of in vivo peroxynitrite-mediated Tyr nitroxidation and cross-linking that lead to the formation of 3-nitrotyrosine and dityrosine, respectively. Peroxynitrite and nitrogen dioxide radicals have been coloured in purple in order to highlight their participation in the process. The nitro group of 3-NT and the new bond resulting from dityrosine formation have been also coloured in purple to highlight their formation. Full article ">Figure 2
Impact of Tyr nitroxidation on the αS-bound α-helical folding. Panels (A,C–E) show the overlapping of the CD spectra of 20 µM αS alone or in the presence of 10 mM SDS (A), 5 mM DOPC-SUVs (C), 5 mM DOPS-SUVs (D), or 5 mM ESC-SUVs (E) on that corresponding to αS-NO2 in the presence of those different lipids. All the CD spectra were acquired in 20 mM phosphate buffer (pH 7.4) enriched with 150 mM NaCl and at 25 °C. Panel (B) shows the percentage of α-helicity achieved for αS (black) and αS-NO2 (purple) in the absence or presence of SDS micelles and distinct SUVs. By using Equation (2), the percentages were determined from the CD data. Full article ">Figure 3
CD study of the effect of temperature on the α-helicities of αS and αS-NO2. (A,B) Overlapping of the CD spectra of solutions containing αS (20 μM) (A) or aS-NO2 (20 μM) (B) in the presence of SDS (10 mM) collected at different temperatures (10–50 °C). (C,D) Plots of the values of [θ]222nm (C) or [θ]200nm (D) collected at different temperatures for solutions containing αS (20 μM) and SDS (10 mM) (black) or αS-NO2 (20 μM) and SDS (10 mM) (purple). In Panels (C,D), the experimental data are shown as dots, whereas their fits to linear functions are shown as lines. Full article ">Figure 4
Study of the impact of Tyr nitroxidation on the affinity of αS-ESC-SUV. (A) Overlapping of the 1H,15N-HSQC spectra of 135 µM αS-NO2 before (black) and after (red) the addition of 1.3 mM ESC-SUVs. Both spectra were acquired in 20 mM phosphate buffer (pH 6.5) at 37 °C. (B) Fractional signal attenuation of the 1H,15N-HSQC signals relative to the lipid-free spectrum as a function of the residue number for αS-NO2 (135 µM) in the presence of ESC-SUVs at 250 µM (black), 610 µM (grey), and 1.3 mM (red) concentrations. The experiments were acquired at 12.5 °C. (C) Lipid-bound fraction of αS-NO2 at increasing ESC-SUV concentrations. The data were obtained from the 1H,15N-HSQC spectra αS-NO2 in the presence of different concentrations of ESC-SUVs (0–30 mM). The spectra were recorded in 20 mM phosphate buffer (pH 6.5) at 12.5 °C. The experimental data were fit to the bimolecular binding curve (Equation (6)) by using the software Sigma Plot (version 10), which allowed obtaining the dissociation constant (Kd). Full article ">Figure 5
Impact of Tyr nitroxidation on the chemical shifts of αS bound to SDS micelles. (A) Overlapping of the 1H,15N-HSQC spectra of 130 µM αS-NO2 (purple) and 100 µM αS (black) obtained in the presence of 40 mM d25-SDS micelles. The spectra were collected in 20 mM phosphate buffer (pH 6.5) at 37 °C. Residues whose signals were shifted as a result of Tyr nitroxidation are labelled in red. (B) Amide chemical shift perturbations (Δδ) of the HN and N backbone resonances of SDS bound-αS as a result of Tyr nitroxidation. For each residue, <math display="inline"><semantics> <mrow> <mo>∆</mo> <mi>δ</mi> <mo>=</mo> <msqrt> <msup> <mrow> <mfenced separators="|"> <mrow> <msub> <mrow> <mo>∆</mo> <mi>δ</mi> </mrow> <mrow> <mi>H</mi> <mi>N</mi> </mrow> </msub> </mrow> </mfenced> </mrow> <mrow> <mn>2</mn> </mrow> </msup> <mo>+</mo> <msup> <mrow> <mi>x</mi> <mo>·</mo> <mfenced separators="|"> <mrow> <msub> <mrow> <mo>∆</mo> <mi>δ</mi> </mrow> <mrow> <mi>N</mi> </mrow> </msub> </mrow> </mfenced> </mrow> <mrow> <mn>2</mn> </mrow> </msup> </msqrt> </mrow> </semantics></math>, where x is 0.2 for Gly and 0.14 for the other residues. ΔδHN and ΔδN are the amide proton and the amide nitrogen chemical shift differences between αS and αS-NO2 in the presence of SDS (Δδx = δx,αSNO2 − δx,αS). The chemical shift assignments of HN and N resonances of the SDS bound αS were achieved in a previous work of our group [<a href="#B11-antioxidants-12-01310" class="html-bibr">11</a>]. Data corresponding to Tyr residues are colored in green. (C) Residue-specific ncSPC α-helical scores (<a href="https://st-protein02.chem.au.dk/ncSPC/" target="_blank">https://st-protein02.chem.au.dk/ncSPC/</a>) (accessed on 7 July 2022) obtained for αS (black and grey) and for αS-NO2 (purple) in the absence (grey) or in the presence (black and purple) of SDS calculated from the HN, Hα, Cα, Cβ, and CO chemical shifts. Here, “+1” denotes the highest propensity to form a completely formed α-helix, “0” denotes disorder, and “−1” denotes a fully formed β-sheet. Full article ">Figure 6
SDS micelle-bound αS-NO2: structure and dynamics. (A) NMR bundles of the 10 lowest-energy structures of αS-NO2 (left). Purple sticks represent the backbone. Average structure of αS-NO2 (right) obtained from the ensemble (left) using MOLMOL. For visualization purposes, the disordered C-terminal domain was deleted in both representations. (B) Alignment of the D2-G41 (H1; (bottom)) and E46-L100 (H2; (top)) regions of the average structures of αS (grey) [<a href="#B11-antioxidants-12-01310" class="html-bibr">11</a>] and αS-NO2 (purple). The Pymol software (version 2.5.3) was used to carry out the alignment. The side chains of Y39 in αS and αS-NO2 are shown as sticks. (C) Plot of the R2 (s−1) relaxation data collected for αS (black) and αS-NO2 (purple) in the presence of SDS micelles. Relaxation values of the different Tyr residues are colored in green. The relaxation measurements were performed at 37 °C in 20 mM phosphate buffer (pH 6.5). Full article ">Figure 7
Studying the impact of Tyr nitroxidation on the ability of αS to modulate the ordering and fusion of SUVs mimicking SVs. (A,B) Lipid order parameters (S) of 130 µM DOPS-SUVs labelled with the TMA-DPH ((A), 2 µM) or DPH ((B), 1 µM) probes in the absence (grey) or in the presence of αS (black) or αS-NO2 (purple). In Panels (A,B), empty and full bars represent the S values of the DOPS-SUVs before and after the addition of 13 µM αS or αS-NO2, respectively. (C,D) DLS size distributions of 130 µM DOPS-SUVs before (red) and after (green) 96 h of incubation with αS (13 µM) (C) or αS-NO2 (13 µM) (D). All the measurements were performed in Buffer B1 and at 25 °C. Full article ">

23 pages, 1667 KiB

Open AccessReview

Benefits of Natural Antioxidants on Oral Health

by Giuseppina Malcangi, Assunta Patano, Anna Maria Ciocia, Anna Netti, Fabio Viapiano, Irene Palumbo, Irma Trilli, Mariafrancesca Guglielmo, Alessio Danilo Inchingolo, Gianna Dipalma, Francesco Inchingolo, Elio Minetti and Angelo Michele Inchingolo

Antioxidants 2023, 12(6), 1309; https://doi.org/10.3390/antiox12061309 - 20 Jun 2023

Cited by 10 | Viewed by 3658

Abstract

In recent years, special attention has been paid to the correlation between oxidation–reduction mechanisms and human health. The free radicals produced via physiological cellular biochemical processes are major contributors to oxidation phenomena. Their instability is the major cause of cellular damage. Free radical [...] Read more.

In recent years, special attention has been paid to the correlation between oxidation–reduction mechanisms and human health. The free radicals produced via physiological cellular biochemical processes are major contributors to oxidation phenomena. Their instability is the major cause of cellular damage. Free radical reactive oxygen species containing oxygen are the best-known ones. The body neutralises the harmful effects of free radicals via the production of endogenous antioxidants (superoxide dismutase, catalase, glutathione, and melatonin). The field of study of nutraucetics has found antioxidant capacity in substances such as vitamins A, B, C, E, coenzyme Q-10, selenium, flavonoids, lipoic acid, carotenoids, and lycopene contained in some foods. There are several areas of investigation that aim to research the interaction between reactive oxygen species, exogenous antioxidants, and the microbiota to promote increased protection via the peroxidation of macromolecules (proteins, and lipids) by maintaining a dynamic balance among the species that make up the microbiota. In this scoping review, we aim to map the scientific literature on oxidative stress related to the oral microbiota, and the use of natural antioxidants to counteract it, to assess the volume, nature, characteristics, and type of studies available to date, and to suggest the possible gaps that will emerge from the analysis. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidant Systems in Oral Health)

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19 pages, 2520 KiB

Open AccessArticle

In Vitro Characterization of Antioxidant, Antibacterial and Antimutagenic Activities of the Green Microalga Ettlia pseudoalveolaris

by Andrea Vornoli, Teresa Grande, Valter Lubrano, Francesco Vizzarri, Chiara Gorelli, Andrea Raffaelli, Clara Maria Della Croce, Santiago Zarate Baca, Carla Sandoval, Vincenzo Longo, Luisa Pozzo and Cristina Echeverria

Antioxidants 2023, 12(6), 1308; https://doi.org/10.3390/antiox12061308 - 20 Jun 2023

Cited by 3 | Viewed by 1792

Abstract

Recently, green microalgae have gained importance due to their nutritional and bioactive compounds, which makes them some of the most promising and innovative functional foods. The aim of this study was to evaluate the chemical profile and the in vitro antioxidant, antimicrobial and [...] Read more.

Recently, green microalgae have gained importance due to their nutritional and bioactive compounds, which makes them some of the most promising and innovative functional foods. The aim of this study was to evaluate the chemical profile and the in vitro antioxidant, antimicrobial and antimutagenic activity of an aqueous extract of the green microalga Ettlia pseudoalveolaris, obtained from the freshwater lakes of the Ecuadorian Highlands. Human microvascular endothelial cells (HMEC-1) were used to determine the ability of the microalga to reduce the endothelial damage caused by hydrogen peroxide-induced oxidative stress. Furthermore, the eukaryotic system Saccharomyces cerevisiae was used to evaluate the possible cytotoxic, mutagenic and antimutagenic effect of E. pseudoalveolaris. The extract showed a notable antioxidant capacity and a moderate antibacterial activity mostly due to the high content in polyphenolic compounds. It is likely that the antioxidant compounds present in the extract were also responsible for the observed reduction in endothelial damage of HMEC-1 cells. An antimutagenic effect through a direct antioxidant mechanism was also found. Based on the results of in vitro assays, E. pseudoalveolaris proved to be a good source of bioactive compounds and antioxidant, antibacterial and antimutagenic capacities making it a potential functional food. Full article

(This article belongs to the Special Issue Antioxidants in Nutraceuticals and Functional Foods: Challenges and Perspectives on Future Nutrition)

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16 pages, 5419 KiB

Open AccessArticle

3-Bromo-4,5-dihydroxybenzaldehyde Protects Keratinocytes from Particulate Matter 2.5-Induced Damages

by Ao-Xuan Zhen, Mei-Jing Piao, Kyoung-Ah Kang, Pincha-Devage-Sameera-Madushan Fernando, Herath-Mudiyanselage-Udari-Lakmini Herath, Suk-Ju Cho and Jin-Won Hyun

Antioxidants 2023, 12(6), 1307; https://doi.org/10.3390/antiox12061307 - 20 Jun 2023

Cited by 3 | Viewed by 1473

Abstract

Cellular senescence can be activated by several stimuli, including ultraviolet radiation and air pollutants. This study aimed to evaluate the protective effect of marine algae compound 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on particulate matter 2.5 (PM_2.5)-induced skin cell damage in vitro and in vivo. [...] Read more.

Cellular senescence can be activated by several stimuli, including ultraviolet radiation and air pollutants. This study aimed to evaluate the protective effect of marine algae compound 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on particulate matter 2.5 (PM_2.5)-induced skin cell damage in vitro and in vivo. The human HaCaT keratinocyte was pre-treated with 3-BDB and then with PM_2.5. PM_2.5-induced reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial dysfunction, DNA damage, cell cycle arrest, apoptotic protein expression, and cellular senescence were measured using confocal microscopy, flow cytometry, and Western blot. The present study exhibited PM_2.5-generated ROS, DNA damage, inflammation, and senescence. However, 3-BDB ameliorated PM_2.5-induced ROS generation, mitochondria dysfunction, and DNA damage. Furthermore, 3-BDB reversed the PM_2.5-induced cell cycle arrest and apoptosis, reduced cellular inflammation, and mitigated cellular senescence in vitro and in vivo. Moreover, the mitogen-activated protein kinase signaling pathway and activator protein 1 activated by PM_2.5 were inhibited by 3-BDB. Thus, 3-BDB suppressed skin damage induced by PM_2.5. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution)

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20 pages, 2855 KiB

Open AccessArticle

Comparative Analysis of Hot and Cold Brews from Single-Estate Teas (Camellia sinensis) Grown across Europe: An Emerging Specialty Product

by Patricia Carloni, Alfonso Albacete, Purificación A. Martínez-Melgarejo, Federico Girolametti, Cristina Truzzi and Elisabetta Damiani

Antioxidants 2023, 12(6), 1306; https://doi.org/10.3390/antiox12061306 - 20 Jun 2023

Cited by 6 | Viewed by 3627

Abstract

Tea is grown around the world under extremely diverse geographic and climatic conditions, namely, in China, India, the Far East and Africa. However, recently, growing tea also appears to be feasible in many regions of Europe, from where high-quality, chemical-free, organic, single-estate teas [...] Read more.

Tea is grown around the world under extremely diverse geographic and climatic conditions, namely, in China, India, the Far East and Africa. However, recently, growing tea also appears to be feasible in many regions of Europe, from where high-quality, chemical-free, organic, single-estate teas have been obtained. Hence, the aim of this study was to characterize the health-promoting properties in terms of the antioxidant capacity of traditional hot brews as well as cold brews of black, green and white teas produced across the European territory using a panel of antioxidant assays. Total polyphenol/flavonoid contents and metal chelating activity were also determined. For differentiating the characteristics of the different tea brews, ultraviolet-visible (UV-Vis) spectroscopy and ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry were employed. Overall, our findings demonstrate for the first time that teas grown in Europe are good quality teas that are endowed with levels of health-promoting polyphenols and flavonoids and that have an antioxidant capacity similar to those grown in other parts of the world. This research is a vital contribution to the characterization of European teas, providing essential and important information for both European tea growers and consumers, and could be of guidance and support for the selection of teas grown in the old continent, along with having the best brewing conditions for maximizing the health benefits of tea. Full article

(This article belongs to the Special Issue Antioxidative Ingredients for Oxidative Stress Prevention: The Potential of Coffee and Tea)

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Figure 1
Graphical distribution of tea micro-plantations across Europe (teacups). The fuchsia teacups indicate the origin of the teas that were studied in this work. Full article ">Figure 2
Total polyphenol content (TPC) of the tea brews measured using Folin-Ciocalteu’s reagent. Bars are colored according to the type of tea (brown = black tea; green = green tea; grey = white tea) and the type of infusion (light shade = cold brew; dark shade = hot brew). The letters above the bars indicate the homogeneous sub-classes resulting from Tukey’s post hoc multiple comparison tests (p < 0.05). Neth. = The Netherlands; Switz. = Switzerland. Full article ">Figure 3
Antioxidant activity of the tea brews measured with the ORAC assay. Bars are colored according to the type of tea (brown = black tea; green = green tea; grey = white tea) and the type of brew (light shade = cold brew; dark shade = hot brew). The letters above the bars indicate the homogeneous sub-classes resulting from Tukey’s post hoc multiple comparison tests (p < 0.05). Neth. = The Netherlands; Switz. = Switzerland. Full article ">Figure 4
The metal chelating activity of the tea brews measured with the ferrozine assay. Bars are colored according to the type of tea (brown = black tea; green = green tea; grey = white tea) and the type of brew (light shade = cold brew; dark shade = hot brew). The. letters above the bars indicate the homogeneous sub-classes resulting from Tukey’s post hoc multiple comparison tests (p < 0.05). Neth. = The Netherlands; Switz. = Switzerland. Full article ">Figure 5
Averaged UV-Vis spectra (320–500 nm, Δλ = 5 nm) of the various cold and hot tea brews. Spectra are colored according to the type of tea (red = black tea; green = green tea; grey = white tea) and the type of infusion (light shade = cold brew; dark shade = hot brew). Full article ">Figure 6
Score plots for the first two components resulting from the principal component analysis performed using the UV-Vis data (320–500 nm, Δλ = 5 nm) of the cold and hot brews. Dots are colored according to the type of tea (brown = black tea; green = green tea; grey = white tea) and the type of infusion (light shade = cold brew; dark shade = hot brew). Full article ">Figure 7
Score plots by multigroup analysis and loading plot for the first two components resulting from the principal component analysis performed using the pairwise jobs of the metabolomic data of the green tea cold brews. Full article ">

15 pages, 4257 KiB

Open AccessArticle

Hepatic Anti-Oxidative Genes CAT and GPX4 Are Epigenetically Modulated by RORγ/NRF2 in Alphacoronavirus-Exposed Piglets

by Haotian Gu, Yaya Liu, Yahui Zhao, Huan Qu, Yanhua Li, Abdelkareem A. Ahmed, Hao-Yu Liu, Ping Hu and Demin Cai

Antioxidants 2023, 12(6), 1305; https://doi.org/10.3390/antiox12061305 - 19 Jun 2023

Cited by 2 | Viewed by 2236

Abstract

As a member of alpha-coronaviruses, PEDV could lead to severe diarrhea and dehydration in newborn piglets. Given that lipid peroxides in the liver are key mediators of cell proliferation and death, the role and regulation of endogenous lipid peroxide metabolism in response to [...] Read more.

As a member of alpha-coronaviruses, PEDV could lead to severe diarrhea and dehydration in newborn piglets. Given that lipid peroxides in the liver are key mediators of cell proliferation and death, the role and regulation of endogenous lipid peroxide metabolism in response to coronavirus infection need to be illuminated. The enzymatic activities of SOD, CAT, mitochondrial complex-I, complex-III, and complex-V, along with the glutathione and ATP contents, were significantly decreased in the liver of PEDV piglets. In contrast, the lipid peroxidation biomarkers, malondialdehyde, and ROS were markedly elevated. Moreover, we found that the peroxisome metabolism was inhibited by the PEDV infection using transcriptome analysis. These down-regulated anti-oxidative genes, including GPX4, CAT, SOD1, SOD2, GCLC, and SLC7A11, were further validated by qRT-PCR and immunoblotting. Because the nuclear receptor RORγ-driven MVA pathway is critical for LPO, we provided new evidence that RORγ also controlled the genes CAT and GPX4 involved in peroxisome metabolism in the PEDV piglets. We found that RORγ directly binds to these two genes using ChIP-seq and ChIP-qPCR analysis, where PEDV strongly repressed the binding enrichments. The occupancies of histone active marks such as H3K9/27ac and H3K4me1/2, together with active co-factor p300 and polymerase II at the locus of CAT and GPX4, were significantly decreased. Importantly, PEDV infection disrupted the physical association between RORγ and NRF2, facilitating the down-regulation of the CAT and GPX4 genes at the transcriptional levels. RORγ is a potential factor in modulating the CAT and GPX4 gene expressions in the liver of PEDV piglets by interacting with NRF2 and histone modifications. Full article

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Figure 1
Oxidative stress was observed after being infected by PEDV. (A,B) The activities of anti–oxidant enzymes SOD and CAT were analyzed and normalized to tissue weight. (C,D) The contents of GSH and MDA were analyzed and normalized to tissue weight. (E) The relative ROS in the PEDV–infected piglets were analyzed. (F–I) The relative parameters of mitochondria ATP, enzyme complex–I, complex–III, and complex–V were analyzed. (*) p < 0.05, (**) p < 0.01 and (***) p < 0.001 compared with the uninfected sample. The circles represent distribution of results for different samples. Full article ">Figure 2
The transcriptional profiling showed that the anti–oxidative pathway was modulated by PEDV infection. (A) Gene ontology (GO) analysis showed that the anti–oxidative metabolic process is one of the most enriched pathways. (B) Volcano plot for the hepatic transcriptome of anti–oxidation measured by RNA–seq analysis. (C) The GSEA plot of the differentially expressed genes in the anti–oxidative pathway of the two groups. FDR, false–discovery rate. Full article ">Figure 3
The expressions of genes included in anti–oxidation and fatty acid oxidation are inhibited by PEDV. (A) Heatmap of mRNA expression changes of the anti–oxidant metabolism genes from the data of RNA–seq. (B) The qRT–PCR analysis confirmed the mRNA expression changes of the anti–oxidant metabolism genes after being infected by PEDV. (C) Heatmap of mRNA expression changes of the fatty acid oxidation genes from the data of RNA–seq. (*) p < 0.05 compared with the uninfected sample. The circles represent distribution of results for different samples. Full article ">Figure 4
The expressions of RORγ and NRF2 in livers were dysregulated after being infected by PEDV. (A,B) Fragments Per Kilobase of transcript per Million mapped reads of RORC (encoding RORγ) and NRF2 were measured by RNA–seq and the mRNA expressions were measured by qRT–PCR. (C,D) The expression of RORγ and NRF2 at the protein level was evaluated via Western blotting. The intensity of these two proteins was normalized to GAPDH protein contents. (*) p < 0.05 and (***) p < 0.001 compared with the uninfected sample. The circles represent distribution of results for different samples. Full article ">Figure 5
RORγ binding occupancies were reduced in the PEDV piglets. (A) ChIP–seq profiles (top) and heatmaps of ChIP–seq signal intensity (bottom) of RORγ within ±10 kb windows around the center of peak regions. (B) ChIP–seq signal visualization of RORγ at representative anti–oxidant metabolism genes CAT and GPX4, the numbers coupled with the group names of Uninfected or PEDV represent the maximum range of data. (C) Schematic diagram depicting the putative RORE sequence on the enhancers of CAT and GPX4. Full article ">Figure 6
PEDV infection decreased the enrichment of RORγ and NRF2 at target loci of CAT and GPX4 genes and their physical interaction. (A–D) ChIP–qPCR analyses of RORγ and NRF2 occupancies at the locus of CAT, GPX4, SOD2, and GSS, normalized to IgG. (E,F) ChIP–re–ChIP analysis of the combined binding of RORγ and NRF2 at the locus of CAT and GPX4. (*) p < 0.05 and (***) p < 0.001 compared with the uninfected sample. The circles represent distribution of results for different samples. Full article ">Figure 7
PEDV infection modifies histone modification at the locus of CAT and GPX4. (A–F) The relative enrichment of histone marks’ (H3K4me1/2/3, H3K9ac, H3K18ac, H3K27ac) occupancy was analyzed by ChIP–qPCR. (G,H) The relative enrichment of co–activator p300 and RNA polymerase II at the locus of CAT and GPX4. (*) p < 0.05 and (***) p < 0.001 compared with the uninfected sample. The circles represent distribution of results for different samples. Full article ">

16 pages, 4519 KiB

Open AccessArticle

Glycolysis Aids in Human Lens Epithelial Cells’ Adaptation to Hypoxia

by Yuxin Huang, Xiyuan Ping, Yilei Cui, Hao Yang, Jing Bao, Qichuan Yin, Hailaiti Ailifeire and Xingchao Shentu

Antioxidants 2023, 12(6), 1304; https://doi.org/10.3390/antiox12061304 - 19 Jun 2023

Cited by 2 | Viewed by 1650

Abstract

Hypoxic environments are known to trigger pathological damage in multiple cellular subtypes. Interestingly, the lens is a naturally hypoxic tissue, with glycolysis serving as its main source of energy. Hypoxia is essential for maintaining the long-term transparency of the lens in addition to [...] Read more.

Hypoxic environments are known to trigger pathological damage in multiple cellular subtypes. Interestingly, the lens is a naturally hypoxic tissue, with glycolysis serving as its main source of energy. Hypoxia is essential for maintaining the long-term transparency of the lens in addition to avoiding nuclear cataracts. Herein, we explore the complex mechanisms by which lens epithelial cells adapt to hypoxic conditions while maintaining their normal growth and metabolic activity. Our data show that the glycolysis pathway is significantly upregulated during human lens epithelial (HLE) cells exposure to hypoxia. The inhibition of glycolysis under hypoxic conditions incited endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production in HLE cells, leading to cellular apoptosis. After ATP was replenished, the damage to the cells was not completely recovered, and ER stress, ROS production, and cell apoptosis still occurred. These results suggest that glycolysis not only performs energy metabolism in the process of HLE cells adapting to hypoxia, but also helps them continuously resist cell apoptosis caused by ER stress and ROS production. Furthermore, our proteomic atlas provides possible rescue mechanisms for cellular damage caused by hypoxia. Full article

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Figure 1
HLE cells adapt to a hypoxic environment. (A) Light photomicrographs of HLECs under hypoxic and normoxic conditions. Scale bars: 500 μm. (B) CCK8 assay was used to detect the cell viability, and the optical density (OD) value of the hypoxia and normoxia conditions showed no statistically significant change. Cell viability is expressed as the mean ± standard deviation of three independent experiments (ns: p > 0.05). (C) Schematic diagram of the proteomics process. Full article ">Figure 2
Proteomic profiles of HLE cells under hypoxia and normoxia conditions. TMT-based proteomic analysis on HLECs subjected to either hypoxia (HYP) or normoxia (CON) conditions. (A) Volcano analysis representing the significantly differentially expressed proteins (DEPs). (B) The heatmap demonstrates that expression patterns were altered under hypoxia. Each column represents a sample, and each row represents the expression levels of a single proteomic in various samples. The colour scale of the heatmap ranges from blue (low expression) to red (high expression). Top 10 enrichment analysis of GO terms for the differentially expressed proteins. The upregulated protein terms (C) in the biological process (BP), cellular component (CC), and molecular function (MF) categories are depicted. (D) KEGG based on upregulated differentially expressed proteins (DEPs) annotated based on proteomic analysis. Full article ">Figure 3
Validation of glycolysis pathway in HLE cells. Images represent protein levels of glycolysis-related proteins in HLECs under hypoxia and normoxia conditions. The protein levels of HK1, HK2, PGK1, ENO2, and LDHA were analysed via Western blot (A). (B) Bar graph shows quantification. Results are combined data from four experiments with different cell preparations, and each value represents mean ± SEM; *: p < 0.05, **: p < 0.01, ns: p > 0.05. (C) Light photomicrographs of HLECs cultured with or without glycolysis inhibitor 2DG under hypoxia conditions. Scale bars: 500 μm. (D) CCK8 assay was used to detect the cell viability and the optical density (OD) values of HLECs; those cultured with glycolysis inhibitor 2DG have significantly lower values under hypoxia conditions. Images represent protein levels of glycolysis-related proteins in HLECs cultured with or without glycolysis inhibitor 2DG under hypoxia conditions (***: p < 0.001). The protein levels of HK1, HK2, PGK1, ENO2, and LDHA were analysed via Western blot (E). (F) Bar graph shows quantification. Results are combined data from four experiments with different cell preparations, and each value represents mean ± SEM; *: p < 0.05, **: p < 0.01, ns: p > 0.05. Full article ">Figure 4
Inhibition of glycolysis induced the upregulation of ROS-, ER stress-, and apoptosis-related proteins. The expression of ER stress markers (GRP94, GRP78, CHOP, XBP1), ROS markers (NRF2, NOX4, SOD1, CAT), and apoptosis markers (BCL2, BAX, CYCS, CASP1, CASP3, CASP4, CASP7, CASP8, CASP9) in HLECs was measured after culturing with or without glycolysis inhibitor 2-deoxyglucose (2DG) under hypoxia conditions by qRT-PCR (A–C). Images represent protein levels of ER stress markers, apoptosis markers, and ROS markers in HLECs cultured with or without glycolysis inhibitor 2-deoxyglucose (2DG) under hypoxia conditions (D,F,H). The protein levels of GRP78, CHOP, XBP1, NRF2, NOX4, CASP3, CASP4, CASP9, and CYCS were analysed via Western blot; bar graph shows quantification (E,G,I). Results are combined data from four experiments with different cell preparations, and each value represents mean ± SEM; *: p < 0.05, **: p < 0.01. Full article ">Figure 5
Inhibition of glycolysis induced ROS, ER stress, and apoptosis. (A) Representative immunofluorescence images of GRP78 (red), CHOP (red), XBP1 (green), and DAPI (blue) in HLE cells treated or untreated with 2DG under a hypoxia environment (magnification 40×). Scale bars: 50 μm. (B) The average fluorescence intensities of GRP78, CHOP, and XBP1 in immunofluorescence experiments (n = 3, >30 cells per experiment, *: p < 0.05, **: p < 0.01). (C,D) Representative fluorescence images depicting the intracellular Annexin V-FITC and ROS levels of HLE cells treated or untreated with 2DG under a hypoxia environment (magnification 40×). Scale bars: 100 μm. (E) The average fluorescence intensities of Annexin V-FITC and ROS in HLE cells (n = 3, >30 cells per experiment, *: p < 0.05). Full article ">Figure 6
Replenishing ATP did not rescue damage caused by glycolytic inhibition in HLE cells. (A) Representative immunofluorescence images of GRP78 (green), CHOP (green), XBP1 (red), and DAPI (blue) in HLE cells treated with 2DG/2DG + ATP or untreated under a hypoxia environment (magnification 40×). Scale bars: 50 μm. (B) The average fluorescence intensities of GRP78, CHOP, and XBP1 in immunofluorescence experiments (n = 3, >30 cells per experiment, *: p < 0.05, **: p < 0.01). (C,D) Representative fluorescence images depicting the intracellular Annexin V-FITC and ROS levels of HLE cells treated with 2DG/2DG + ATP or untreated with 2DG under a hypoxia environment (magnification 40×). Scale bars: 100 μm. (E) The average fluorescence intensities of Annexin V-FITC and ROS in HLE cells (n = 3, >30 cells per experiment, *: p < 0.05, **: p < 0.01). Full article ">

23 pages, 4966 KiB

Open AccessArticle

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

by Rocío Muñoz-García, Marina Sánchez-Hidalgo, Manuel Alcarranza, María Victoria Vazquéz-Román, María Alvarez de Sotomayor, María Luisa González-Rodríguez, María C. de Andrés and Catalina Alarcón-de-la-Lastra

Antioxidants 2023, 12(6), 1303; https://doi.org/10.3390/antiox12061303 - 19 Jun 2023

Cited by 1 | Viewed by 1808

Abstract

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main [...] Read more.

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response. Full article

(This article belongs to the Special Issue Olive Tree Products and Antioxidants)

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Graphical abstract

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Full article ">Figure 1
Immunomodulatory effect of an OLA-supplemented diet on the weight of the spleen and thymus organs 6 months after pristane induction. Data are expressed as the mean ± SEM (n = 10). One-way ANOVA followed by Tukey’s post hoc test results: ## p < 0.01 vs. naïve control group; * p < 0.05 vs. SD-pristane group. Full article ">Figure 2
Histological effects of OLA dietary treatment on pristane-induced SLE mice. Representative images of (A–C) H&E staining; (D–F) PAS, and (G–I) MT stains from renal tissues from mice. Normal histology architecture in the cortex and medullary renal naïve mice with low stroma between renal tubules (A,G) and normal glomeruli in the cortex parenchyma (D, arrows). Compressed glomeruli in SD-Pristane mice (B, arrows), probably due to Bowman space proliferation with the partial sclerosis of glomerular tufts. Inflammatory cells occupying the medullary interstitium (E, arrows). Fibrotic tissue characterized by an abundance of collagen along with hemorrhagic signs identified in the medullary stroma (H). OLA-treated mice showed no histopathological changes either in the medullary or renal cortex. Normal distribution of renal tubules in medullary parenchyma (C), two glomeruli showing regular size and shape (F, arrows), and a renal cortex with no fibrosis or pathologic changes (I). Scale bar, 25 µm (A–I). Scale bar, 100 µm (H black-dotted squared). Full article ">Figure 3
An OLA-supplemented diet reduced IgG and IgM deposits in the kidney tissue of pristane-induced SLE mice. Representative figures of (A–F) IHC and (G–L) IF staining of IgG or IgM in kidneys from pristane-induced SLE mice. (A,D,G,J) Absence of deposits of IgG and IgM in the naïve group. (B,E,H,K) Marked IgG and IgM deposits in the renal glomeruli of SD-pristane mice. (B,E, black arrows) Deposits in the capillary loops and mesangial cells and into the tubular interstices (extraglomerular nephritis). Deposits in capillary loops (H, white arrow) and mesangial deposits (H, yellow arrow) (mesangio—capillary glomerulonephritis). They were also accompanied by extraglomerular deposits. Mesangial glomerulonephritis (K, yellow arrow) also appeared with intracapillary deposits (K, white arrow) and tubular involvement. Scale bar, 25 µm. Full article ">Figure 4
Dietary OLA administration reduced COX-2, iNOS, and mPGES-1 protein overexpression. Protein expression was measured in total kidney homogenates from mice. Densitometry was performed after normalization to the control (β-actin housekeeping gene). One-way ANOVA followed by Tukey’s post hoc test results: ## p < 0.01, ### p < 0.001 vs. naïve group; ** p < 0.01, *** p < 0.001 vs. SD-pristane group. Data were represented as the mean ± SEM (n = 6). Full article ">Figure 5
Role of the OLA dietary treatment in the regulation of SLE-related intracellular signaling pathways. Protein expressions of (A) phosphorylated JAK3/STAT-3; (B) the Nrf-2/HO-1 axis; (C) the IκB-α and p65/p50 nuclear subunits, and (D) phosphorylated P38, JNK, and ERK MAPKs were evaluated in renal homogenates from mice. Densitometry was performed after normalization to the control (JNK, ERK, p38, or β-actin). Data are represented as the means ± SEM (n = 6). One-way ANOVA followed by Tukey’s post hoc test results: # p < 0.05, ## p < 0.01, ### p < 0.001 vs. naïve group; * p < 0.05, ** p < 0.01, *** p < 0.001 significant difference versus SD-pristane group. Full article ">Figure 6
The inflammasome signaling pathway was downregulated by an OLA-supplemented diet. (A) NLRP3/ASC, (B) Caspase 11, (C) IL-18, and (D) Caspase 1. Protein expressions were analyzed by immunoblots in kidney lysates. Densitometry was performed following normalization to the control (β-actin housekeeping gene). Data are represented as the means ± SEM (n = 6). One-way analysis of variance (ANOVA), using Tukey–Kramer multiple comparisons test as post hoc test: # p < 0.05, ## p < 0.01, ### p < 0.001 vs. naïve group; * p < 0.05 ** p < 0.01; significant difference versus SD-pristane group. Full article ">Figure 7
The OLA-supplemented diet enhanced redox-sensitive effectors and endothelial function in pristane-induced mice. (B) NOX-1 and (C) penos Thr495 protein expression quantification in homogenates of aortic rings from mice. Data are represented as the mean ± SEM (n = 6). β-Actin was used as a loading control. One-way ANOVA followed by Tukey’s post hoc test results: # p < 0.05, ### p < 0.001 vs. naïve group; * p < 0.05, vs. SD-pristane group. (A) Endothelial relaxation was induced by ACh (0.001–10 mM) in U46619 (0.003 mM) precontracted intact aorta rings from mice. The Ach-induced relaxant responses are expressed as a percentage of precontraction induced by U46619 (n = 7 per group). One-way ANOVA followed by Fisher’s LSD test results: * p < 0.05; ** p < 0.01 significant difference versus naïve control group (U46619), thromboxane receptor agonist 9,11-didesoxi-11α,9α-epoximetanoprostaglandina F2α. Full article ">Figure 8
OLA dietary treatment modulated miRNAs and dnmt1 expression in pristane-induced nephritis. The relative renal expression of miRNAs: (A) miRNA-23b, (B) miRNA-146a, (C) miRNA-24-3p, and (D) miRNA-126, as well as (E) DNMT-1 mRNA from mice of the naïve, SD-pristane, and OLA-enriched diet groups, evaluated by RT-qPCR. Expression was normalized with MammU6 or β-actin, (n = 8). One-way ANOVA followed by Tukey’s post hoc test results: # p < 0.05, ## p < 0.01; ### p < 0.001 vs. naïve group; * p < 0,05, ** p < 0.01; *** p < 0.001, significant difference versus SD-pristane group. Full article ">

13 pages, 1236 KiB

Open AccessReview

Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells—An Issue Still Open

by Giulia Paties Montagner, Silvia Dominici, Simona Piaggi, Alfonso Pompella and Alessandro Corti

Antioxidants 2023, 12(6), 1302; https://doi.org/10.3390/antiox12061302 - 19 Jun 2023

Cited by 4 | Viewed by 1821

Abstract

Boric acid (BA) is the dominant form of boron in plasma, playing a role in different physiological mechanisms such as cell replication. Toxic effects have been reported, both for high doses of boron and its deficiency. Contrasting results were, however, reported about the [...] Read more.

Boric acid (BA) is the dominant form of boron in plasma, playing a role in different physiological mechanisms such as cell replication. Toxic effects have been reported, both for high doses of boron and its deficiency. Contrasting results were, however, reported about the cytotoxicity of pharmacological BA concentrations on cancer cells. The aim of this review is to briefly summarize the main findings in the field ranging from the proposed mechanisms of BA uptake and actions to its effects on cancer cells. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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18 pages, 7027 KiB

Open AccessArticle

Phaeanthus vietnamensis Ban Ameliorates Lower Airway Inflammation in Experimental Asthmatic Mouse Model via Nrf2/HO-1 and MAPK Signaling Pathway

by Thi Van Nguyen, Chau Tuan Vo, Van Minh Vo, Cong Thuy Tram Nguyen, Thi My Pham, Chun Hua Piao, Yan Jing Fan, Ok Hee Chai and Thi Tho Bui

Antioxidants 2023, 12(6), 1301; https://doi.org/10.3390/antiox12061301 - 19 Jun 2023

Cited by 1 | Viewed by 1740

Abstract

Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. Phaeanthus vietnamensis BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant, anti-microbial, anti-inflammatory potential, and gastro-protective properties. However, there is no study about P. vietnamensis [...] Read more.

Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. Phaeanthus vietnamensis BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant, anti-microbial, anti-inflammatory potential, and gastro-protective properties. However, there is no study about P. vietnamensis extract (PVE) on asthma disease. Here, an OVA-induced asthma mouse model was established to evaluate the anti-inflammatory and anti-asthmatic effects and possible mechanisms of PVE. BALB/c mice were sensitized by injecting 50 μg OVA into the peritoneal and challenged by nebulization with 5% OVA. Mice were orally administered various doses of PVE once daily (50, 100, 200 mg/kg) or dexamethasone (Dex; 2.5 mg/kg) or Saline 1 h before the OVA challenge. The cell infiltrated in the bronchoalveolar lavage fluid (BALF) was analyzed; levels of OVA-specific immunoglobulins in serum, cytokines, and transcription factors in the BALF were measured, and lung histopathology was evaluated. PVE, especially PVE 200mg/kg dose, could improve asthma exacerbation by balancing the Th1/Th2 ratio, reducing inflammatory cells in BALF, depressing serum anti-specific OVA IgE, anti-specific OVA IgG1, histamine levels, and retrieving lung histology. Moreover, the PVE treatment group significantly increased the expressions of antioxidant enzymes Nrf2 and HO-1 in the lung tissue and the level of those antioxidant enzymes in the BALF, decreasing the oxidative stress marker MDA level in the BALF, leading to the relieving the activation of MAPK signaling in asthmatic condition. The present study demonstrated that Phaeanthus vietnamensis BÂN, traditionally used in Vietnam as a medicinal plant, may be used as an efficacious agent for treating asthmatic disease. Full article

(This article belongs to the Special Issue Oxidative Stress and Lung Inflammation)

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12 pages, 1004 KiB

Open AccessReview

Effect of 8-Hydroxyguanine DNA Glycosylase 1 on the Function of Immune Cells

by Weiran Zhang, Ranwei Zhong, Xiangping Qu, Yang Xiang and Ming Ji

Antioxidants 2023, 12(6), 1300; https://doi.org/10.3390/antiox12061300 - 19 Jun 2023

Cited by 1 | Viewed by 1834

Abstract

Excess reactive oxygen species (ROS) can cause an imbalance between oxidation and anti-oxidation, leading to the occurrence of oxidative stress in the body. The most common product of ROS-induced base damage is 8-hydroxyguanine (8-oxoG). Failure to promptly remove 8-oxoG often causes mutations during [...] Read more.

Excess reactive oxygen species (ROS) can cause an imbalance between oxidation and anti-oxidation, leading to the occurrence of oxidative stress in the body. The most common product of ROS-induced base damage is 8-hydroxyguanine (8-oxoG). Failure to promptly remove 8-oxoG often causes mutations during DNA replication. 8-oxoG is cleared from cells by the 8-oxoG DNA glycosylase 1 (OGG1)-mediated oxidative damage base excision repair pathway so as to prevent cells from suffering dysfunction due to oxidative stress. Physiological immune homeostasis and, in particular, immune cell function are vulnerable to oxidative stress. Evidence suggests that inflammation, aging, cancer, and other diseases are related to an imbalance in immune homeostasis caused by oxidative stress. However, the role of the OGG1-mediated oxidative damage repair pathway in the activation and maintenance of immune cell function is unknown. This review summarizes the current understanding of the effect of OGG1 on immune cell function. Full article

(This article belongs to the Special Issue Cellular ROS and Antioxidants: Physiological and Pathological Role)

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11 pages, 2739 KiB

Open AccessCommunication

Relationships between Serum Biomarkers of Oxidative Stress and Tobacco Smoke Exposure in Patients with Mental Disorders

by Ana-Maria Vlasceanu, Daniela Gradinaru, Miriana Stan, Viorela G. Nitescu and Daniela Luiza Baconi

Antioxidants 2023, 12(6), 1299; https://doi.org/10.3390/antiox12061299 - 19 Jun 2023

Viewed by 2947

Abstract

The role of cigarette smoking as an aggravating factor of systemic oxidative stress in patients with mental disorders has not been extensively investigated, although significantly higher rates of smoking are recorded in these subjects in comparison with the general population. In the present [...] Read more.

The role of cigarette smoking as an aggravating factor of systemic oxidative stress in patients with mental disorders has not been extensively investigated, although significantly higher rates of smoking are recorded in these subjects in comparison with the general population. In the present study, we tested the hypothesis that smoking might be an exacerbator of systemic oxidative stress, being directly correlated with the degree of exposure to tobacco smoke. We analyzed, in 76 adult subjects from a public health care unit, the relationships between serum cotinine levels as a marker of tobacco smoke exposure, and three biomarkers of oxidative stress: the serum glutathione (GSH), the advanced oxidation protein products (AOPPs), and the total serum antioxidant status (FRAP). The results indicate that the degree of tobacco smoke exposure was inversely associated with GSH levels in both passive and active smokers, suggesting that smoke particulate components’ toxicity is associated with a systemic GSH depletion. Paradoxically, the lowest AOPP levels which were positively associated with GSH, were recorded in active smoking patients whereas in passive smokers individual values of AOPPs decreased along with the increase in GSH levels. Our data suggest that an enhanced inhalation of particulate constituents of cigarette smoke could induce critical changes in systemic redox homeostasis and GSH can no longer exert its antioxidant role. Full article

(This article belongs to the Special Issue Cigarette Smoking: Associated Oxidative Stress and Health Hazards)

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27 pages, 5786 KiB

Open AccessArticle

Antioxidant Activities of Photoinduced Phycogenic Silver Nanoparticles and Their Potential Applications

by Vijayakumar Maduraimuthu, Jayappriyan Kothilmozhian Ranishree, Raja Mohan Gopalakrishnan, Brabakaran Ayyadurai, Rathinam Raja and Klaus Heese

Antioxidants 2023, 12(6), 1298; https://doi.org/10.3390/antiox12061298 - 18 Jun 2023

Cited by 9 | Viewed by 2676

Abstract

While various methods exist for synthesizing silver nanoparticles (AgNPs), green synthesis has emerged as a promising approach due to its affordability, sustainability, and suitability for biomedical purposes. However, green synthesis is time-consuming, necessitating the development of efficient and cost-effective techniques to minimize reaction [...] Read more.

While various methods exist for synthesizing silver nanoparticles (AgNPs), green synthesis has emerged as a promising approach due to its affordability, sustainability, and suitability for biomedical purposes. However, green synthesis is time-consuming, necessitating the development of efficient and cost-effective techniques to minimize reaction time. Consequently, researchers have turned their attention to photo-driven processes. In this study, we present the photoinduced bioreduction of silver nitrate (AgNO₃) to AgNPs using an aqueous extract of Ulva lactuca, an edible green seaweed. The phytochemicals found in the seaweed functioned as both reducing and capping agents, while light served as a catalyst for biosynthesis. We explored the effects of different light intensities and wavelengths, the initial pH of the reaction mixture, and the exposure time on the biosynthesis of AgNPs. Confirmation of AgNP formation was achieved through the observation of a surface plasmon resonance band at 428 nm using an ultraviolet-visible (UV-vis) spectrophotometer. Fourier transform infrared spectroscopy (FTIR) revealed the presence of algae-derived phytochemicals bound to the outer surface of the synthesized AgNPs. Additionally, high-resolution transmission electron microscopy (HRTEM) and atomic force microscopy (AFM) images demonstrated that the NPs possessed a nearly spherical shape, ranging in size from 5 nm to 40 nm. The crystalline nature of the NPs was confirmed by selected area electron diffraction (SAED) and X-ray diffraction (XRD), with Bragg’s diffraction pattern revealing peaks at 2θ = 38°, 44°, 64°, and 77°, corresponding to the planes of silver 111, 200, 220, and 311 in the face-centered cubic crystal lattice of metallic silver. Energy-dispersive X-ray spectroscopy (EDX) results exhibited a prominent peak at 3 keV, indicating an Ag elemental configuration. The highly negative zeta potential values provided further confirmation of the stability of AgNPs. Moreover, the reduction kinetics observed via UV-vis spectrophotometry demonstrated superior photocatalytic activity in the degradation of hazardous pollutant dyes, such as rhodamine B, methylene orange, Congo red, acridine orange, and Coomassie brilliant blue G-250. Consequently, our biosynthesized AgNPs hold great potential for various biomedical redox reaction applications. Full article

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15 pages, 1348 KiB

Open AccessArticle

Anti-Inflammatory, Anti-Oxidative and Anti-Apoptotic Effects of Thymol and 24-Epibrassinolide in Zebrafish Larvae

by Germano A. B. Lanzarin, Luís M. Félix, Sandra M. Monteiro, Jorge M. Ferreira, Paula A. Oliveira and Carlos Venâncio

Antioxidants 2023, 12(6), 1297; https://doi.org/10.3390/antiox12061297 - 18 Jun 2023

Cited by 3 | Viewed by 1952

Abstract

Thymol (THY) and 24-epibrassinolide (24-EPI) are two examples of plant-based products with promising therapeutic effects. In this study, we investigated the anti-inflammatory, antioxidant and anti-apoptotic effects of the THY and 24-EPI. We used zebrafish (Danio rerio) larvae transgenic line (Tg(mpx [...] Read more.

Thymol (THY) and 24-epibrassinolide (24-EPI) are two examples of plant-based products with promising therapeutic effects. In this study, we investigated the anti-inflammatory, antioxidant and anti-apoptotic effects of the THY and 24-EPI. We used zebrafish (Danio rerio) larvae transgenic line (Tg(mpxGFP)ⁱ¹¹⁴) to evaluate the recruitment of neutrophils as an inflammatory marker to the site of injury after tail fin amputation. In another experiment, wild-type AB larvae were exposed to a well known pro-inflammatory substance, copper (CuSO4), and then exposed for 4 h to THY, 24-EPI or diclofenac (DIC), a known anti-inflammatory drug. In this model, the antioxidant (levels of reactive oxygen species—ROS) and anti-apoptotic (cell death) effects were evaluated in vivo, as well as biochemical parameters such as the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), the biotransformation activity of glutathione-S-transferase, the levels of glutathione reduced and oxidated, lipid peroxidation, acetylcholinesterase activity, lactate dehydrogenase activity, and levels of nitric acid (NO). Both compounds decreased the recruitment of neutrophils in Tg(mpxGFP)ⁱ¹¹⁴, as well as showed in vivo antioxidant effects by reducing ROS production and anti-apoptotic effects in addition to a decrease in NO compared to CuSO4. The observed data substantiate the potential of the natural compounds THY and 24-EPI as anti-inflammatory and antioxidant agents in this species. These results support the need for further research to understand the molecular pathways involved, particularly their effect on NO. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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Treatment effects on neutrophil migration to the lesion site in zebrafish larvae (Tg(mpxGFP)i114) produced by tail transection. (A) Diagram of the experimental design for the neutrophil migration (B) Image of a normal Tg(mpxGFP)i114 zebrafish larva (control), and a larva with tail transection (Control cut) and detailed photos of the transection site after 4 h of treatment. The scale bar represents 125 μm. (C) Graph showing the normalized number of neutrophils that migrated to the tail after 4 hpi (Mean of control: 30.7 ± 9.2). Data are expressed as mean ± SD from at least five independent samples from five random animals each. Different letters represent statistical differences among treatment groups (p < 0.05). Full article ">Figure 2
Effect of different treatments on cell death and ROS production in zebrafish WT larvae with 72 hpf exposed for 4 h. Data from at least five independent samples from twenty-five random animals each. (A) Schematic diagram showing the experimental exposure protocol for the study of cell death and ROS production. (B) Illustrative images from larvae exposed to the DCF probe. (C) Illustrative images from larvae exposed to the AO probe. (D) Result of the DCF fluorescence intensities in homogenized larvae (Mean of control: 37.9 ± 8.8). (E) Result of AO fluorescence intensities in homogenized larvae (Mean of control: 48.4 ± 7.5). Data are expressed as mean ± SD and normalized according to the control group. Different letters represent statistical differences among treatment groups (p < 0.05). Full article ">Figure 3
Biochemical indicators were examined in 72-hour-old zebrafish WT larvae subjected to various treatments for 4 h. (A) Schematic diagram of the experimental methodology for biochemical marker exposure and analysis. (B) Graphs of biochemical indicators that differed significantly following exposure to various treatments. Data were obtained from at least five independent samples from fifty random animals each and values normalized to the control group. Data are expressed as median (interquartile range) for non-parametric data (Median of control: SOD = 7.2 (6.3–7.9) U/mg.protein) or mean ± SD for parametric data distribution (Mean of control: CAT = 2.9 ± 0.9 U/mg.protein; GPx = 2.24 ± 0.3 nmol NADPH/min.mg protein; OSI = 0.18 ± 0.05; AChE = 10.43 ± 1.96 μmol TNB/min.mg protein; LDH = 65.45 ± 5.15 nmol NADH/min.mg protein; NO = 23.4 ± 11.3 nmol NO/mg protein). Different letters represent statistical differences among treatment groups (p < 0.05). Full article ">

16 pages, 1796 KiB

Open AccessArticle

Effect of Exercise Repetitions on Arylesterase Activity of PON1 in Plasma of Average-Trained Men—The Dissociation between Activity and Concentration

by Aneta Otocka-Kmiecik, Monika Orłowska-Majdak, Robert Stawski, Urszula Szkudlarek, Gianluca Padula, Szymon Gałczyński and Dariusz Nowak

Antioxidants 2023, 12(6), 1296; https://doi.org/10.3390/antiox12061296 - 17 Jun 2023

Viewed by 1550

Abstract

Exercise may increase the antioxidant capacity of plasma by stimulating antioxidant enzymes. The study aimed to measure the effect of three repetitions of acute exercise on arylesterase (ARE) activity of the paraoxonase 1 (PON1) enzyme. Eleven average-trained men (age 34.0 ± 5.2 years) [...] Read more.

Exercise may increase the antioxidant capacity of plasma by stimulating antioxidant enzymes. The study aimed to measure the effect of three repetitions of acute exercise on arylesterase (ARE) activity of the paraoxonase 1 (PON1) enzyme. Eleven average-trained men (age 34.0 ± 5.2 years) completed three treadmill runs. ARE activity in plasma was evaluated spectrophotometrically and compared with PON1 concentration (PON1c), paraoxonase (PON) activity, and high-density lipoprotein cholesterol (HDL-C) at rest and after exercise. In all repetitions of the exercise, ARE activity remained stable, and ARE activity standardized for PON1c (ARE/PON1c) was lower post- than pre-exercise. The ARE/PON1c ratio changes returned to baseline levels during rest after each exercise session. Pre-exercise ARE activity correlated negatively with post-exercise C-reactive protein (CRP) (ρ = −0.35, p = 0.049), white blood cell count (WBC) (ρ = −0.35, p = 0.048), polymorphonuclear leukocytes (PMN) (ρ = −0.37, p = 0.037), and creatine kinase (CK) (ρ = −0.37, p = 0.036). ARE activity may be depleted under conditions of oxidative stress, as increases in PON1c during acute exercise did not result in parallel increases in ARE activity. No adaptation of the response of ARE activity to exercise was detected in subsequent exercise sessions. Individuals with lower pre-exercise ARE activity may develop a higher inflammatory response to strenuous exercise. Full article

(This article belongs to the Special Issue Exercise-Induced Oxidative Stress in Health and Disease)

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Plausible mechanisms of reversible increase in PON1 concentration with concomitant decrease in ARE activity in plasma during acute exercise. <img alt="Antioxidants 12 01296 i001" src="/antioxidants/antioxidants-12-01296/article_deploy/html/images/antioxidants-12-01296-i001.png"/>-increase, <img alt="Antioxidants 12 01296 i002" src="/antioxidants/antioxidants-12-01296/article_deploy/html/images/antioxidants-12-01296-i002.png"/>- decrease, PON1—paraoxonase 1, HDL—high-density lipoprotein, ROS—reactive oxygen species, Ca2+—catalytic calcium ion in the active site tunnel of PON1, His—Histidine, Cys—Cysteine, -SH groups—sulfhydryl groups. Full article ">Figure 2
Flowchart of the study. BP—blood pressure measurement, ECG—electrocardiography, VO2max—maximal oxygen consumption. Full article ">Figure 3
No significant effect of repeated exercise on arylesterase activity (ARE) of paraoxonase 1 (PON1) in the plasma of average-trained men (mean ± SD). Full article ">Figure 4
Effect of repeated exercise on arylesterase to paraoxonase 1 concentration ratio (ARE/PON1c) in the plasma of average-trained men (mean ± SD). * vs. corresponding pre-exercise value, p < 0.05. Full article ">Figure 5
Scatterplot of variables x and y. Correlation of pre-exercise values of arylesterase (ARE) activity and post-exercise C-reactive protein (CRP) in the plasma of average-trained men. Pooled individual data from three exercise bouts (n = 33; ρ = −0.35, p = 0.049). Full article ">

19 pages, 1245 KiB

Open AccessReview

The Influence of Antioxidants on Oxidative Stress-Induced Vascular Aging in Obesity

by Hiva Sharebiani, Shayan Keramat, Abdolali Chavoshan, Bahar Fazeli and Agata Stanek

Antioxidants 2023, 12(6), 1295; https://doi.org/10.3390/antiox12061295 - 17 Jun 2023

Cited by 5 | Viewed by 1912

Abstract

Obesity is a worldwide trend that is growing in incidence very fast. Adipose tissue dysfunction caused by obesity is associated with the generation of oxidative stress. Obesity-induced oxidative stress and inflammation play a key role in the pathogenesis of vascular diseases. Vascular aging [...] Read more.

Obesity is a worldwide trend that is growing in incidence very fast. Adipose tissue dysfunction caused by obesity is associated with the generation of oxidative stress. Obesity-induced oxidative stress and inflammation play a key role in the pathogenesis of vascular diseases. Vascular aging is one of the main pathogenesis mechanisms. The aim of this study is to review the effect of antioxidants on vascular aging caused by oxidative stress in obesity. In order to achieve this aim, this paper is designed to review obesity-caused adipose tissue remodeling, vascular aging generated by high levels of oxidative stress, and the effects of antioxidants on obesity, redox balance, and vascular aging. It seems that vascular diseases in obese individuals are complex networks of pathological mechanisms. In order to develop a proper therapeutic tool, first, there is a need for a better understanding of interactions between obesity, oxidative stress, and aging. Based on these interactions, this review suggests different lines of strategies that include change in lifestyle to prevent and control obesity, strategies for adipose tissue remodelling, oxidant–antioxidant balance, inflammation suppression, and strategies against vascular aging. Some antioxidants support different lines of these strategies, making them appropriate for complex conditions such as oxidative stress-induced vascular diseases in obese individuals. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammation and Organ Damage in Health and Disease--State of Art)

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13 pages, 1522 KiB

Open AccessReview

Revised Aspects into the Molecular Bases of Hydroxycinnamic Acid Metabolism in Lactobacilli

by Félix López de Felipe

Antioxidants 2023, 12(6), 1294; https://doi.org/10.3390/antiox12061294 - 17 Jun 2023

Cited by 3 | Viewed by 1754

Abstract

Hydroxycinnamic acids (HCAs) are phenolic compounds produced by the secondary metabolism of edible plants and are the most abundant phenolic acids in our diet. The antimicrobial capacity of HCAs is an important function attributed to these phenolic acids in the defense of plants [...] Read more.

Hydroxycinnamic acids (HCAs) are phenolic compounds produced by the secondary metabolism of edible plants and are the most abundant phenolic acids in our diet. The antimicrobial capacity of HCAs is an important function attributed to these phenolic acids in the defense of plants against microbiological threats, and bacteria have developed diverse mechanisms to counter the antimicrobial stress imposed by these compounds, including their metabolism into different microbial derivatives. The metabolism of HCAs has been intensively studied in Lactobacillus spp., as the metabolic transformation of HCAs by these bacteria contributes to the biological activity of these acids in plant and human habitats or to improve the nutritional quality of fermented foods. The main mechanisms known to date used by Lactobacillus spp. to metabolize HCAs are enzymatic decarboxylation and/or reduction. Here, recent advances in the knowledge regarding the enzymes that contribute to these two enzymatic conversions, the genes involved, their regulation and the physiological significance to lactobacilli are reviewed and critically discussed. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Graphic representation of metabolic decarboxylation of caffeic, p-coumaric and ferulic acid into their corresponding vinyl derivatives by Lactobacillus spp. The predicted pKa of the hydroxycinnamic acids and their vinyl derivatives are shown. Each vinyl derivative shares the same R group as the hydroxycinnamic acid from which it is derived; PAD, phenolic acid decarboxylase. Full article ">Figure 2
Genetic organization of the L. plantarum WCFS1 chromosomal regions containing clusters harboring genetically and biochemically validated genes determining hydroxycinnamate metabolic conversions: hydroxycinnamate decarboxylation padA or lp_3665 (red arrow) (A) [NCBI accession NC_004567; lp_3663 (or usp1) through lp_3665 (or padA)]; hydroxycinnamate reduction hcrB or lp_1425 (green arrow) (B) [NCBI accession NC_004567; lp_1422 (or hcrR) through lp_1426 (or hcrC)] or vinylphenol reduction vprA or lp_3125 (blue arrow) (C) [NCBI accession NC_004567; lp_3124 (or vprR) through lp_3125 (or vprA)]. Lys-R type regulators that control decarboxylation or reduction of hydroxycinnamates as well as the reduction of vinylphenols, are indicated by lined arrows. Full article ">Figure 3
Graphic representation of metabolic reduction of vinyl derivatives of caffeic (vinylcatechol), p-coumaric (vinylphenol) and ferulic (vinylguaicol) acids by Lactobacillus spp. Each ethyl derivative shares the same R group as the vinyl derivative from which it is derived. VprA, vinylphenol reductase A. Full article ">Figure 4
Graphic representation of metabolic reduction of caffeic, p-coumaric and ferulic acid into phenylpropionic derivatives by Lactobacillus spp. HcrB, hydroxycinnamate reductase B. Each phenylpropionic acid shares the same R group as the hydroxycinnamic acid from which it is derived. Full article ">

20 pages, 2434 KiB

Open AccessArticle

Improvement of Fresh Ovine “Tuma” Cheese Quality Characteristics by Application of Oregano Essential Oils

by Giuliana Garofalo, Marialetizia Ponte, Carlo Greco, Marcella Barbera, Michele Massimo Mammano, Giancarlo Fascella, Giuseppe Greco, Giulia Salsi, Santo Orlando, Antonio Alfonzo, Antonino Di Grigoli, Daniela Piazzese, Adriana Bonanno, Luca Settanni and Raimondo Gaglio

Antioxidants 2023, 12(6), 1293; https://doi.org/10.3390/antiox12061293 - 17 Jun 2023

Cited by 5 | Viewed by 1570

Abstract

In the present work, oregano essential oils (OEOs) were applied to process the fresh ovine cheese “Tuma” obtained by pressed cheese technology. Cheese making trials were performed under industrial conditions using ewe’s pasteurized milk and two strains of Lactococcus lactis (NT1 and NT4) [...] Read more.

In the present work, oregano essential oils (OEOs) were applied to process the fresh ovine cheese “Tuma” obtained by pressed cheese technology. Cheese making trials were performed under industrial conditions using ewe’s pasteurized milk and two strains of Lactococcus lactis (NT1 and NT4) as fermenting agents. Two experimental cheese products (ECP) were obtained through the addition of 100 (ECP100) and 200 (ECP200) µL/L of OEO to milk, while the control cheese product (CCP) was OEO-free. Both Lc. lactis strains showed in vitro and in vivo ability to grow in the presence of OEOs and to dominate over indigenous milk lactic acid bacteria (LAB) resistant to pasteurization. In the presence of OEOs, the most abundant compound found in cheese was carvacrol, constituting more than 65% of the volatile fraction in both experimental products. The addition of OEOs did not influence ash, fat, or protein content, but it increased by 43% the antioxidant capacity of the experimental cheeses. ECP100 cheeses showed the best appreciation scores by the sensory panel. In order to investigate the ability OEOs to be used as a natural preservative, a test of artificial contamination was carried out, and the results showed a significant reduction of the main dairy pathogens in OEO-added cheeses. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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23 pages, 6215 KiB

Open AccessFeature PaperArticle

A Deadly Liaison between Oxidative Injury and p53 Drives Methyl-Gallate-Induced Autophagy and Apoptosis in HCT116 Colon Cancer Cells

by Antonietta Notaro, Marianna Lauricella, Diana Di Liberto, Sonia Emanuele, Michela Giuliano, Alessandro Attanzio, Luisa Tesoriere, Daniela Carlisi, Mario Allegra, Anna De Blasio, Giuseppe Calvaruso and Antonella D’Anneo

Antioxidants 2023, 12(6), 1292; https://doi.org/10.3390/antiox12061292 - 16 Jun 2023

Cited by 6 | Viewed by 1784

Abstract

Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it [...] Read more.

Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it was found to be ineffective on differentiated Caco-2 cells, which is a model of polarized colon cells. In the first phase of treatment, MG promoted both early ROS generation and endoplasmic reticulum (ER) stress, sustained by elevated PERK, Grp78 and CHOP expression levels, as well as an upregulation in intracellular calcium content. Such events were accompanied by an autophagic process (16–24 h), where prolonging the time (48 h) of MG exposure led to cellular homeostasis collapse and apoptotic cell death with DNA fragmentation and p53 and γH2Ax activation. Our data demonstrated that a crucial role in the MG-induced mechanism is played by p53. Its level, which increased precociously (4 h) in MG-treated cells, was tightly intertwined with oxidative injury. Indeed, the addition of N-acetylcysteine (NAC), which is a ROS scavenger, counteracted the p53 increase, as well as the MG effect on cell viability. Moreover, MG promoted p53 accumulation into the nucleus and its inhibition by pifithrin-α (PFT-α), which is a negative modulator of p53 transcriptional activity, enhanced autophagy, increased the LC3-II level and inhibited apoptotic cell death. These findings provide new clues to the potential action of MG as a possible anti-tumor phytomolecule for colon cancer treatment. Full article

(This article belongs to the Special Issue Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants)

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15 pages, 2098 KiB

Open AccessArticle

Red Quinoa Hydrolysates with Antioxidant Properties Improve Cardiovascular Health in Spontaneously Hypertensive Rats

by Miguel López-Moreno, Estefanía Jiménez-Moreno, Antonio Márquez Gallego, Gema Vera Pasamontes, José Antonio Uranga Ocio, Marta Garcés-Rimón and Marta Miguel-Castro

Antioxidants 2023, 12(6), 1291; https://doi.org/10.3390/antiox12061291 - 16 Jun 2023

Cited by 7 | Viewed by 2158

Abstract

In recent years, quinoa has been postulated as an emerging crop for the production of functional foods. Quinoa has been used to obtain plant protein hydrolysates with in vitro biological activity. The aim of the present study was to evaluate the beneficial effect [...] Read more.

In recent years, quinoa has been postulated as an emerging crop for the production of functional foods. Quinoa has been used to obtain plant protein hydrolysates with in vitro biological activity. The aim of the present study was to evaluate the beneficial effect of red quinoa hydrolysate (QrH) on oxidative stress and cardiovascular health in an in vivo experimental model of hypertension (HTN) in the spontaneously hypertensive rat (SHR). The oral administration of QrH at 1000 mg/kg/day (QrHH) showed a significant reduction in SBP from baseline (−9.8 ± 4.5 mm Hg; p < 0.05) in SHR. The mechanical stimulation thresholds did not change during the study QrH groups, whereas in the case of SHR control and SHR vitamin C, a significant reduction was observed (p < 0.05). The SHR QrHH exhibited higher antioxidant capacity in the kidney than the other experimental groups (p < 0.05). The SHR QrHH group showed an increase in reduced glutathione levels in the liver compared to the SHR control group (p < 0.05). In relation to lipid peroxidation, SHR QrHH exhibited a significant decrease in plasma, kidney and heart malondialdehyde (MDA) values compared to the SHR control group (p < 0.05). The results obtained revealed the in vivo antioxidant effect of QrH and its ability to ameliorate HTN and its associated complications. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Cardiovascular Health)

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Main modifiable and non-modifiable risk factors that can increase the likelihood of developing CVDs and hypertension. Full article ">Figure 2
Body weight gain at the end of the treatment. Data represent mean values ± standard error of the mean (SEM) for each group. One-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences (p < 0.05). Full article ">Figure 3
Evolution of water intake in the different experimental groups during the study. Data represent mean values ± standard error of the mean (SEM) for each group. Two-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">Figure 4
Increase in systolic blood pressure (SBP) in the different experimental groups during the 8-week experimental period. Data represent mean values ± standard error of the mean (SEM) for each group. One-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">Figure 5
Mechanical stimulation threshold at weeks 2, 6 and 10 of the study, using the Von Frey filament test. Data represent mean values ± standard error of the mean (SEM) for each group. Two-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">Figure 6
Antioxidant capacity of kidney assessed by oxygen radical absorbance capacity (ORAC). Data represent mean values ± standard error of the mean (SEM) for each group. One-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">Figure 7
Reduced glutathione levels in the liver of the different experimental groups. Data represent mean values ± standard error of the mean (SEM) for each group. One-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">Figure 8
Malondialdehyde (MDA) concentration in plasma (a), heart (b) and kidney (c) at the end of the experimental period. Data represent mean values ± standard error of the mean (SEM) for each group. One-way ANOVA followed by Bonferroni post hoc test. Different letters indicate significant differences between groups (p < 0.05). Full article ">

20 pages, 1060 KiB

Open AccessReview

Insights into the Role of Plasmatic and Exosomal microRNAs in Oxidative Stress-Related Metabolic Diseases

by Ayauly Duisenbek, Gabriela C. Lopez-Armas, Miguel Pérez, María D. Avilés Pérez, José Miguel Aguilar Benitez, Víctor Roger Pereira Pérez, Juan Gorts Ortega, Arailym Yessenbekova, Nurzhanyat Ablaikhanova, Germaine Escames, Darío Acuña-Castroviejo and Iryna Rusanova

Antioxidants 2023, 12(6), 1290; https://doi.org/10.3390/antiox12061290 - 16 Jun 2023

Cited by 5 | Viewed by 2057

Abstract

A common denominator of metabolic diseases, including type 2 diabetes Mellitus, dyslipidemia, and atherosclerosis, are elevated oxidative stress and chronic inflammation. These complex, multi-factorial diseases are caused by the detrimental interaction between the individual genetic background and multiple environmental stimuli. The cells, including [...] Read more.

A common denominator of metabolic diseases, including type 2 diabetes Mellitus, dyslipidemia, and atherosclerosis, are elevated oxidative stress and chronic inflammation. These complex, multi-factorial diseases are caused by the detrimental interaction between the individual genetic background and multiple environmental stimuli. The cells, including the endothelial ones, acquire a preactivated phenotype and metabolic memory, exhibiting increased oxidative stress, inflammatory gene expression, endothelial vascular activation, and prothrombotic events, leading to vascular complications. There are different pathways involved in the pathogenesis of metabolic diseases, and increased knowledge suggests a role of the activation of the NF-kB pathway and NLRP3 inflammasome as key mediators of metabolic inflammation. Epigenetic-wide associated studies provide new insight into the role of microRNAs in the phenomenon of metabolic memory and the development consequences of vessel damage. In this review, we will focus on the microRNAs related to the control of anti-oxidative enzymes, as well as microRNAs related to the control of mitochondrial functions and inflammation. The objective is the search for new therapeutic targets to improve the functioning of mitochondria and reduce oxidative stress and inflammation, despite the acquired metabolic memory. Full article

(This article belongs to the Special Issue Genetics and Epigenetic Modifications on Metabolic Diseases Oxidative Related)

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Metabolic changes in the endothelial cell. The endogenous increased cytokines act through the Toll-like receptors (TLRs) to activate NF-kB—NLRP3 inflammasome pathway. Under conditions of hyperglycemia, the accumulation of reducing equivalents (NADH+H, FADH2) feeds the respiratory chain with electrons, which leads to greater electron escape and increased superoxide radical (O2−•) production. The increment of polyol pathway leads to Advanced glycation end products (AGEs) accumulation, which act on the AGEs receptors (RAGE), leading to the activation of pro-oxidative enzymes, such as NAD(P)H oxidase, and decrement of NRF2, one important component of the anti-oxidative system of the cell. Increased β-oxidation upon the excess of fatty acid contributes to the accumulation of D-acyl glycerol, thus conducing to the activation of protein kinase C (PKC). The translocation of NF-κB to the nucleus activates the transcription of its target genes, including pro-IL-1, pro-il-18, and Pro-Caspase 1. The activation of NLRP3 inflammasome facilities the cleavage of the pro-Caspase 1 into its active form Caspase1, which in turn transforms IL-1β and IL-18 into their active forms. Subsequently, IL-18 induces the production of TNF-λ, which in turn promotes the synthesis and release of IL-6 and C reactive protein (CRP) (not shown). At the same time, the production of adhesion molecules is activated: vascular adhesion molecule-1 (VCAM-1), platelet-derived grown factor (PDGF), and vascular endothelial grown factor (VEGF). The endoplasmic reticulum (ER) stress contributes to the trigger for NLRP3 inflammasome activation and potentiating oxidative stress. Full article ">Figure 2
Some examples of the exosome’s microRNAs’ participation in the pathogenesis of metabolic diseases. Exosomes derived from adipose tissue macrophages, designated ATM-EXO, isolated from obese mice have been shown to confer insulin resistance and glucose intolerance when injected into lean mice (achieved in miR-155). ATM-derived miR-29 can transfer to myocytes, hepatocytes, and adipocytes, causing insulin resistance in vivo. miR-690, abundant in exosomes of anti-inflammatory M2-like macrophages, repolarized ATM-EXO towards an anti-inflammatory M2-like phenotype. Full article ">

34 pages, 3068 KiB

Open AccessReview

Brain Iron Metabolism, Redox Balance and Neurological Diseases

by Guofen Gao, Linhao You, Jianhua Zhang, Yan-Zhong Chang and Peng Yu

Antioxidants 2023, 12(6), 1289; https://doi.org/10.3390/antiox12061289 - 16 Jun 2023

Cited by 17 | Viewed by 2455

Abstract

The incidence of neurological diseases, such as Parkinson’s disease, Alzheimer’s disease and stroke, is increasing. An increasing number of studies have correlated these diseases with brain iron overload and the resulting oxidative damage. Brain iron deficiency has also been closely linked to neurodevelopment. [...] Read more.

The incidence of neurological diseases, such as Parkinson’s disease, Alzheimer’s disease and stroke, is increasing. An increasing number of studies have correlated these diseases with brain iron overload and the resulting oxidative damage. Brain iron deficiency has also been closely linked to neurodevelopment. These neurological disorders seriously affect the physical and mental health of patients and bring heavy economic burdens to families and society. Therefore, it is important to maintain brain iron homeostasis and to understand the mechanism of brain iron disorders affecting reactive oxygen species (ROS) balance, resulting in neural damage, cell death and, ultimately, leading to the development of disease. Evidence has shown that many therapies targeting brain iron and ROS imbalances have good preventive and therapeutic effects on neurological diseases. This review highlights the molecular mechanisms, pathogenesis and treatment strategies of brain iron metabolism disorders in neurological diseases. Full article

(This article belongs to the Special Issue Iron Metabolism, Redox Balance and Neurological Diseases)

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Figure 1
Roles of different cells in brain iron metabolism. The main route of brain iron uptake is where the iron in the blood crosses the blood–brain barrier (BBB) via Tf-TfR1 in the apical surface of brain microvascular epithelial cells (BMVECs) and FPN1 in the basal surface of BMVECs. Iron can also enter the brain through the transcytosis of ferritin by its receptors at BBB. After iron influxes into the brain parenchymal tissue, it can enter astrocytes through their end feet surrounding BBB and then be transferred to neurons. Iron across the BBB can also directly enter the interstitial fluid of the brain and be transferred to neurons and other cells without passing through astrocytes (see black lines). Astrocytes hepcidin secreted through its end feet to directly decrease FPN1 level of BMVECs, which decreased the iron influx into brain tissues. GPI-CP expressed by astrocytes assists FPN1 in releasing iron into the brain. Astrocyte-specific Cp knockout blocks iron influx FPN1-CP pathway into the brain (see black lines and crosses). Neurons acquire both trivalent and divalent iron through TfR1, TCT1 and DMT1, while those astrocytes that are not part of the BBB acquire iron via DMT1 and ZIP molecules. Oligodendrocytes mainly uptake iron via DMT1 and Tim2. Oligodendrocytes can secrete Tf, while the activated microglia can secrete Lf. Neurons and glia store iron in ferritin and release iron through FPN1 with the coordination of CP/hephaestin or hepcidin, thereby further promoting cross-talk and interaction with other types of cells. Full article ">Figure 2
Interplay between ferroptosis and iron homeostasis. Lipid peroxides that induce ferroptosis are produced through auto-oxidation and/or enzymatic activity of LOX on lipid esters generated from lipids via the activity of ACSL4 and lysophosphatidylcholine acyltransferase 3 (LPCAT3). GPx4 blocks ferroptosis by converting lipid peroxides to lipid alcohols, whereas reductions in GSH or GPx4 activity by blocking of xCT antiporter (e.g., by erastin) or inhibiting of GPx4 (e.g., RSL3) can trigger ferroptosis. The increase in labile iron pool in the cytosol via an increased iron uptake through TfR1 and/or autophagic degradation of ferritin can exacerbate ferroptosis via facilitating lipid peroxidation, and, thus, iron chelators, such as DFO and ROS scavengers (e.g., ferrostatin-1), suppress ferroptosis. Full article ">Figure 3
The interplay of iron and ROS in the pathogenesis of neurological diseases. Dysregulation of iron content in neurological system and the associated generation of ROS participate in the pathological processes of Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, neuropsychiatric disorders and abnormal neurodevelopment. Full article ">Figure 4
Iron accumulation is important in the pathogenesis of PD. Dysregulation of CP, IRP2, Nrf2 and FtMt alters brain iron levels, which, in turn, affects the expression of iron metabolism proteins. Iron overload and increased ROS aggravate the development and progression of PD, and their interactions with α-synuclein, dopamine, neuromelanin, Parkin and LRRK2 contribute to dopaminergic neuronal cell death and the onset of PD. Full article ">Figure 5
Iron accumulation participates in the pathogenesis of AD. Elevated cellular iron is related to Aβ1-42 production and tau phosphorylation. Excessive iron leads to mitochondrial dysfunction. The pre-oxidant effects of iron induce DNA damage and lipid ROS generation, contributing to cell death. Full article ">

15 pages, 3475 KiB

Open AccessArticle

Effect of Copper Sulphate Exposure on the Oxidative Stress, Gill Transcriptome and External Microbiota of Yellow Catfish, Pelteobagrus fulvidraco

by Shun Zhou, Qiuhong Yang, Yi Song, Bo Cheng and Xiaohui Ai

Antioxidants 2023, 12(6), 1288; https://doi.org/10.3390/antiox12061288 - 16 Jun 2023

Cited by 4 | Viewed by 2152

Abstract

This study aimed to investigate the potential adverse effects of the practical application of copper sulfate on yellow catfish (Pelteobagrus fulvidraco) and to provide insights into the gill toxicity induced by copper sulphate. Yellow catfish were exposed to a conventional anthelmintic [...] Read more.

This study aimed to investigate the potential adverse effects of the practical application of copper sulfate on yellow catfish (Pelteobagrus fulvidraco) and to provide insights into the gill toxicity induced by copper sulphate. Yellow catfish were exposed to a conventional anthelmintic concentration of copper sulphate (0.7 mg/L) for seven days. Oxidative stress biomarkers, transcriptome, and external microbiota of gills were examined using enzymatic assays, RNA-sequencing, and 16S rDNA analysis, respectively. Copper sulphate exposure led to oxidative stress and immunosuppression in the gills, with increased levels of oxidative stress biomarkers and altered expression of immune-related differentially expressed genes (DEGs), such as IL-1β, IL4Rα, and CCL24. Key pathways involved in the response included cytokine–cytokine receptor interaction, NOD-like receptor signaling pathway, and Toll-like receptor signaling pathway. The 16S rDNA analysis revealed copper sulphate altered the diversity and composition of gill microbiota, as evidenced by a significant decrease in the abundance of Bacteroidotas and Bdellovibrionota and a significant increase in the abundance of Proteobacteria. Notably, a substantial 8.5-fold increase in the abundance of Plesiomonas was also observed at the genus level. Our findings demonstrated that copper sulphate induced oxidative stress, immunosuppression, and gill microflora dysbiosis in yellow catfish. These findings highlight the need for sustainable management practices and alternative therapeutic strategies in the aquaculture industry to mitigate the adverse effects of copper sulphate on fish and other aquatic organisms. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Summary of differentially expressed genes (DEGs) in gills of yellow catfish (Pelteobagrus fulvidraco) after exposure to 0.7 mg/L copper sulphate. (A) Volcano plot of DEGs. Red and blue dots represent significantly up-regulated and down-regulated DEGs, respectively. (B) Transcriptome analysis of the number and expression of DEGs. Full article ">Figure 2
GO and KEGG enrichment analysis of the differentially expressed genes in the gills of yellow catfish (Pelteobagrus fulvidraco) after exposure to 0.7 mg/L copper sulphate. The vertical axis represents different GO terms (A–C) or pathways (D), and the horizontal axis represents rich factor. Full article ">Figure 3
QRT−PCR verification of differentially expressed genes in the gills of yellow catfish (Pelteobagrus fulvidraco) after exposure to 0.7 mg/L copper sulphate. The X−axis displays 9 DEGs, and the Y−axis represents relative fold change. The data are expressed as the means ± SD (n = 3). Full article ">Figure 4
Simpson index and Shannon index of bacterial communities in the gills of yellow catfish (Pelteobagrus fulvidraco) after exposure to 0.7 mg/L copper sulphate. C: 0 mg/L copper sulphate; T: 0.7 mg/L copper sulphate. Full article ">Figure 5
Relative abundances of dominant microbial phyla (A) and genera (B) in the gills of yellow catfish (Pelteobagrus fulvidraco) after exposure to 0.7 mg/L copper sulphate. C: 0 mg/L copper sulphate; T: 0.7 mg/L copper sulphate. Full article ">Figure 6
(A) The abundance differences in microbial taxa of yellow catfish (Pelteobagrus fulvidraco) between the control group and copper sulphate exposure group at the genus level, ** p < 0.01; (B) KEGG analysis identified various enriched pathways between the control group and copper sulphate exposure group. C: 0 mg/L copper sulphate; T: 0.7 mg/L copper sulphate. Full article ">

14 pages, 5304 KiB

Open AccessArticle

The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr^−/− Mice with Obesity

by Undral Munkhsaikhan, Young In Kwon, Amal M. Sahyoun, María Galán, Alexis A. Gonzalez, Karima Ait-Aissa, Ammaar H. Abidi, Adam Kassan and Modar Kassan

Antioxidants 2023, 12(6), 1287; https://doi.org/10.3390/antiox12061287 - 16 Jun 2023

Viewed by 2348

Abstract

Objectives: Homozygous familial hypercholesteremia (HoFH) is a rare, life-threatening metabolic disease, mainly caused by a mutation in the LDL receptor. If untreated, HoFH causes premature death from acute coronary syndrome. Lomitapide is approved by the FDA as a therapy to lower lipid levels [...] Read more.

Objectives: Homozygous familial hypercholesteremia (HoFH) is a rare, life-threatening metabolic disease, mainly caused by a mutation in the LDL receptor. If untreated, HoFH causes premature death from acute coronary syndrome. Lomitapide is approved by the FDA as a therapy to lower lipid levels in adult patients with HoFH. Nevertheless, the beneficial effect of lomitapide in HoFH models remains to be defined. In this study, we investigated the effect of lomitapide on cardiovascular function using LDL receptor-knockout mice (LDLr⁻/⁻). Methods: Six-week-old LDLr⁻/⁻ mice were fed a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. Lomitapide (1 mg/Kg/Day) was given by oral gavage for the last 2 weeks in the HFD group. Body weight and composition, lipid profile, blood glucose, and atherosclerotic plaques were measured. Vascular reactivity and markers for endothelial function were determined in conductance arteries (thoracic aorta) and resistance arteries (mesenteric resistance arteries (MRA)). Cytokine levels were measured by using the Mesoscale discovery V-Plex assays. Results: Body weight (47.5 ± 1.5 vs. 40.3 ± 1.8 g), % of fat mass (41.6 ± 1.9% vs. 31.8 ± 1.7%), blood glucose (215.5 ± 21.9 vs. 142.3 ± 7.7 mg/dL), and lipid levels (cholesterol: 600.9 ± 23.6 vs. 451.7 ± 33.4 mg/dL; LDL/VLDL: 250.6 ± 28.9 vs. 161.1 ± 12.24 mg/dL; TG: 299.5 ± 24.1 vs. 194.1 ± 28.1 mg/dL) were significantly decreased, and the % of lean mass (56.5 ± 1.8% vs. 65.2 ± 2.1%) was significantly increased in the HFD group after lomitapide treatment. The atherosclerotic plaque area also decreased in the thoracic aorta (7.9 ± 0.5% vs. 5.7 ± 0.1%). After treatment with lomitapide, the endothelium function of the thoracic aorta (47.7 ± 6.3% vs. 80.7 ± 3.1%) and mesenteric resistance artery (66.4 ± 4.3% vs. 79.5 ± 4.6%) was improved in the group of LDLr⁻/⁻ mice on HFD. This was correlated with diminished vascular endoplasmic (ER) reticulum stress, oxidative stress, and inflammation. Conclusions: Treatment with lomitapide improves cardiovascular function and lipid profile and reduces body weight and inflammatory markers in LDLr⁻/⁻ mice on HFD. Full article

(This article belongs to the Special Issue Natural Antioxidants in Obesity and Related Diseases)

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Lomitapide reduced body weight and blood glucose and ameliorated body composition profile in LDLr−/− mice on HFD. Body weight (BW) (A), blood glucose (BG) (B), percentage of fat mass (C), and lean mass (D) in LDLr−/− control mice and mice fed with a high-fat diet (HFD) in the presence and absence of lomitapide treatment (n = 6–10). * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. Full article ">Figure 2
Lomitapide enhanced the lipid profile in LDLr−/− mice on HFD. Total cholesterol (A), LDL/VLDL (B), HDL (C), and TG (D) in plasma from LDLr−/− control mice and mice fed with a high-fat diet (HFD) treated with vehicle or lomitapide (n = 5–6). LDL/VLDL: low-density lipoprotein/very low-density lipoprotein; HDL: high-density lipoprotein; TG: triglyceride. ns > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. Full article ">Figure 3
Oil O Red staining and quantification of plaque lesion area. Lomitapide decreased plaque surface area in the thoracic aorta of LDLr−/− mice with obesity (n = 3). Representative images of en face staining by Oil O red of the entire aorta are shown (A), the whole aorta quantification of the lesion area (B), the aortic arch area (C), and the descending aorta (D). ns > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 assessed by ANOVA followed by the Tukey test for multiple comparisons. Full article ">Figure 4
Lomitapide prevented endothelial dysfunction in the thoracic aorta from LDLr−/− mice on HFD. Endothelium-dependent dilation to Ach (A), endothelium-independent dilation to SNP (B) (n = 11–14), immunoblots showing (T-eNOS, p-eNOS, BIP, CHOP, P65, TNFα, and GAPDH) (C), and quantification (D) in thoracic aorta from LDLr−/− lean mice and LDLr−/− obese mice treated with vehicle or lomitapide (n = 3–6). Ach: acetylcholine; SNP: sodium nitroprusside; T-eNOS: total endothelial nitric oxide synthase; p-eNOS: phosphorylated endothelial nitric oxide synthase; BIP: GRP78; CHOP: he C/EBP homologous protein; P65: NF-kappa-B; TNFα: tumor necrosis factor alpha. ns > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. Full article ">Figure 5
Lomitapide prevented endothelial dysfunction in MRA from LDLr−/− mice on HFD. Endothelium-dependent dilation to Ach (A), endothelium-independent dilation to SNP (B) (n = 11–18), immunoblots showing (T-eNOS, p-eNOS, BIP, CHOP, P65, TNFα, and GAPDH) (C), and quantification (D) in MRA from LDLr−/− lean mice and LDLr−/− obese mice treated with vehicle or lomitapide (n = 3–6). Ach: acetylcholine; SNP: sodium nitroprusside; T-eNOS: total endothelial nitric oxide synthase; p-eNOS: phosphorylated endothelial nitric oxide synthase; BIP: GRP78; CHOP: the C/EBP homologous protein; P65: NF-kappa-B; TNFα: tumor necrosis factor alpha. ns > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. Full article ">Figure 6
Lomitapide treatment downregulated oxidative and endoplasmic reticulum (ER) stress and inflammatory markers in thoracic aorta from LDLr−/− mice on HFD. mRNA levels for ER stress markers (BIP, ATF6, ATF4) (A–C), oxidative stress marker (NOX2) (D), and inflammation markers (NFkB-p65, -p50, TNFα, VCAM1) (E–H) in thoracic aorta from LDLr−/− lean mice and LDLr−/− obese mice treated with vehicle or lomitapide (n = 8–12). BIP: GRP78; ATF6 and ATF4: activating transcription factor; p65 and p50: a subunit of NF-kappa B transcription complex; TNFα: tumor necrosis factor alpha; VCAM1: vascular cell adhesion molecule 1. ns > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. Full article ">Figure 7
Lomitapide treatment showed an anti-inflammatory effect in LDLr−/− mice with obesity. Lomitapide treatment significantly decreased inflammatory cytokines IL-6 (A), KC/GRO (B), and TNFα (C) in LDLr−/− obese mice (n = 12–14). IL-6: interleukin 6; KC/GRO: neutrophil-activating protein 3; TNFα: tumor necrosis factor alpha. ns > 0.05; * p < 0.05; *** p < 0.001; **** p < 0.0001. Full article ">Figure 8
Schema summarizing the findings in this paper. Full article ">

22 pages, 2309 KiB

Open AccessReview

Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases

by Manho Kim, Hyejun Jang, Wijin Kim, Doyeon Kim and Ju Hyun Park

Antioxidants 2023, 12(6), 1286; https://doi.org/10.3390/antiox12061286 - 16 Jun 2023

Cited by 8 | Viewed by 3061

Abstract

Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as [...] Read more.

Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as nucleic acids, lipids, and proteins, and can also be utilized as carriers for drug delivery. However, the low productivity and high cost of mammalian-derived EVs (MDEVs) are major barriers to their practical clinical application where large-scale production is essential. Recently, there has been growing interest in plant-derived EVs (PDEVs) that can produce large amounts of electricity at a low cost. In particular, PDEVs contain plant-derived bioactive molecules such as antioxidants, which are used as therapeutic agents to treat various diseases. In this review, we discuss the composition and characteristics of PDEVs and the appropriate methods for their isolation. We also discuss the potential use of PDEVs containing various plant-derived antioxidants as replacements for conventional antioxidants. Full article

(This article belongs to the Special Issue Plant Materials and Their Antioxidant Potential)

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Schematic of disease development through damage to cellular components of ROS increased by various environmental stresses (created with BioRender.com). Full article ">Figure 2
A schematic diagram for the isolation of EVs from various sources using different isolation methods (created with BioRender.com). Full article ">Figure 3
Effect of ASEVs on chronic skin wounds. (A) A schematic illustration of the ASEVs isolation procedure using the PEG-based precipitation method. (B) Effect of ASEVs on mRNA expression levels of pro-inflammatory cytokines IL-6 and IL-1b in LPS-stimulated RAW 264.7 cells. (C) Proliferation promoting effect of ASEVs in HDFs (*** p < 0.005). Adapted from Ref. [<a href="#B84-antioxidants-12-01286" class="html-bibr">84</a>]. Full article ">Figure 4
Preventive effect of GEVs on colitis-associated cancer (CAC). (A) Structural integrity and morphological characteristics of GEVs confirmed via transmission electron microscopy (TEM) and atomic force microscopy (AFM). (B) Effect of GEVs on inhibition of CAC formation. Colon tumors were obtained at the end of the CAC model mouse induction (* p < 0.05, ** p < 0.01, ns, not significant). Adapted with permission from Ref. [<a href="#B139-antioxidants-12-01286" class="html-bibr">139</a>]. Copyright 2016 Elsevier. Full article ">Figure 5
Inhibitory effect of PLEVs on UV-induced senescence in HaCaT cells. (A) Effect of PLEVs on mRNA expression levels of MMP-1 and COL1A2, markers of aging. (B) Effect of PLEVs on protein expression levels of MMP-1 and COL1A2, markers of aging. (C) Effect of PLEVs on SA-β-Gal levels increased by UV treatment (* p < 0.05, ** p < 0.01). Adapted from Ref. [<a href="#B140-antioxidants-12-01286" class="html-bibr">140</a>]. Full article ">

16 pages, 1479 KiB

Open AccessArticle

From Grape By-Products to Enriched Yogurt Containing Pomace Extract Loaded in Nanotechnological Nutriosomes Tailored for Promoting Gastro-Intestinal Wellness

by Ines Castangia, Federica Fulgheri, Francisco Javier Leyva-Jimenez, Maria Elena Alañón, Maria de la Luz Cádiz-Gurrea, Francesca Marongiu, Maria Cristina Meloni, Matteo Aroffu, Matteo Perra, Mohamad Allaw, Rita Abi Rached, Rodrigo Oliver-Simancas, Elvira Escribano Ferrer, Fabiano Asunis, Maria Letizia Manca and Maria Manconi

Antioxidants 2023, 12(6), 1285; https://doi.org/10.3390/antiox12061285 - 15 Jun 2023

Cited by 2 | Viewed by 1598

Abstract

Grape pomace is the main by-product generated during the winemaking process; since it is still rich in bioactive molecules, especially phenolic compounds with high antioxidant power, its transformation in beneficial and health-promoting foods is an innovative challenge to extend the grape life cycle. [...] Read more.

Grape pomace is the main by-product generated during the winemaking process; since it is still rich in bioactive molecules, especially phenolic compounds with high antioxidant power, its transformation in beneficial and health-promoting foods is an innovative challenge to extend the grape life cycle. Hence, in this work, the phytochemicals still contained in the grape pomace were recovered by an enhanced ultrasound assisted extraction. The extract was incorporated in liposomes prepared with soy lecithin and in nutriosomes obtained combining soy lecithin and Nutriose FM06^®, which were further enriched with gelatin (gelatin-liposomes and gelatin-nutriosomes) to increase the samples’ stability in modulated pH values, as they were designed for yogurt fortification. The vesicles were sized ~100 nm, homogeneously dispersed (polydispersity index < 0.2) and maintained their characteristics when dispersed in fluids at different pH values (6.75, 1.20 and 7.00), simulating salivary, gastric and intestinal environments. The extract loaded vesicles were biocompatible and effectively protected Caco-2 cells against oxidative stress caused by hydrogen peroxide, to a better extent than the free extract in dispersion. The structural integrity of gelatin-nutriosomes, after dilution with milk whey was confirmed, and the addition of vesicles to the yogurt did not modify its appearance. The results pointed out the promising suitability of vesicles loading the phytocomplex obtained from the grape by-product to enrich the yogurt, offering a new and easy strategy for healthy and nutritional food development. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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Representative cryo-TEM images of grape pomace extract loaded liposomes (A), nutriosomes (B), gelatin-liposomes (C) and gelatin-nutriosomes (D). Full article ">Figure 2
(A) Viability of Caco-2 cells incubated for 48 h with grape pomace extract in dispersion or loaded in liposomes, nutriosomes, gelatin-liposomes and gelatin-nutriosomes, diluted at different concentrations (40, 4 and 0.4 µg/mL). Mean values ± standard deviations were reported (n = 8). Same letter (a) indicates not statistically different values (p > 0.05 versus untreated cells) and statistically different from other (p < 0.05 versus other formulations). (B) Viability of Caco-2 cells stressed with hydrogen peroxide (1:40,000) and treated with grape pomace extract (4 µg/mL) in dispersions or loaded in liposomes, nutriosomes, gelatin-liposomes and gelatin-nutriosomes. Mean values ± standard deviations were reported (n = 8). Same letter (a and b) indicates not statistically different values (p > 0.05 versus untreated cells) and statistically different from other (p < 0.05 versus other formulations). Full article ">Figure 3
Viscosity values of yogurt containing different concentrations (0, 5, 10 and 20%) of liposomes, nutriosomes, gelatin-liposomes and gelatin-nutriosomes. Mean values ± standard deviations (error bars) were reported. Same letter (a, b, c, d, e, f, g and h) indicates not statistically different values (p > 0.05), while different letters indicates statistically different values (p < 0.05). Full article ">

16 pages, 10320 KiB

Open AccessArticle

Caffeic Acid, a Polyphenolic Micronutrient Rescues Mice Brains against Aβ-Induced Neurodegeneration and Memory Impairment

by Amjad Khan, Jun Sung Park, Min Hwa Kang, Hyeon Jin Lee, Jawad Ali, Muhammad Tahir, Kyonghwan Choe and Myeong Ok Kim

Antioxidants 2023, 12(6), 1284; https://doi.org/10.3390/antiox12061284 - 15 Jun 2023

Cited by 7 | Viewed by 2159

Abstract

Oxidative stress plays an important role in cognitive dysfunctions and is seen in neurodegeneration and Alzheimer’s disease (AD). It has been reported that the polyphenolic compound caffeic acid possesses strong neuroprotective and antioxidant effects. The current study was conducted to investigate the therapeutic [...] Read more.

Oxidative stress plays an important role in cognitive dysfunctions and is seen in neurodegeneration and Alzheimer’s disease (AD). It has been reported that the polyphenolic compound caffeic acid possesses strong neuroprotective and antioxidant effects. The current study was conducted to investigate the therapeutic potential of caffeic acid against amyloid beta (Aβ_1–42)-induced oxidative stress and memory impairments. Aβ_1–42 (5 μL/5 min/mouse) was administered intracerebroventricularly (ICV) into wild-type adult mice to induce AD-like pathological changes. Caffeic acid was administered orally at 50 mg/kg/day for two weeks to AD mice. Y-maze and Morris water maze (MWM) behavior tests were conducted to assess memory and cognitive abilities. Western blot and immunofluorescence analyses were used for the biochemical analyses. The behavioral results indicated that caffeic acid administration improved spatial learning, memory, and cognitive abilities in AD mice. Reactive oxygen species (ROS) and lipid peroxidation (LPO) assays were performed and showed that the levels of ROS and LPO were markedly reduced in the caffeic acid-treated mice, as compared to Aβ-induced AD mice brains. Moreover, the expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were regulated with the administration of caffeic acid, compared to the Aβ-injected mice. Next, we checked the expression of ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic proteins (GFAP), and other inflammatory markers in the experimental mice, which suggested enhanced expression of these markers in AD mice brains, and were reduced with caffeic acid treatment. Furthermore, caffeic acid enhanced synaptic markers in the AD mice model. Additionally, caffeic acid treatment also decreased Aβ and BACE-1 expression in the Aβ-induced AD mice model. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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