The ability of nanostructures to facilitate the generation of reactive oxygen species and charge carriers underlies many of their chemical and biological activities. Elucidating which factors are essential and how these influence the... more
The ability of nanostructures to facilitate the generation of reactive oxygen species and charge carriers underlies many of their chemical and biological activities. Elucidating which factors are essential and how these influence the production of various active intermediates is fundamental to understanding potential applications of these nanostructures, as well as potential risks. Using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we assessed 3 mixed metal sulfides of varying compositions for their abilities to generate reactive oxygen species, photogenerate electrons, and consume oxygen during photo-irradiation. We found these irradiated mixed metal sulfides exhibited composition dependent generation of ROS: ZnIn2S4 can generate •OH, O2-• and 1O2; CdIn2S4 can produce O2-• and 1O2, while AgInS2 only produces O2-•. Our characterizations of the reactivity of the photogenerated electrons and consumption of dissolved oxygen, performed us...
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EPR saturation-recovery (SR) measurements of the electron spin-lattice relaxation time, T 1, of nitroxide- radical spin probes have been made from 2 to 35 GHz. T1 values of small water-soluble spin probes increase linearly with microwave... more
EPR saturation-recovery (SR) measurements of the electron spin-lattice relaxation time, T 1, of nitroxide- radical spin probes have been made from 2 to 35 GHz. T1 values of small water-soluble spin probes increase linearly with microwave frequency throughout the full range of available frequencies. T1 values of four commonly used hydrophobic probes in lipid bilayers also increase with frequency, but
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Short-pulse saturation recovery electron spin resonance methods have been used to measure lateral diffusion of nitroxide-labeled lipids in multilamellar liposomal dispersions. Nitroxides with 14N and 15N isotopes introduced both... more
Short-pulse saturation recovery electron spin resonance methods have been used to measure lateral diffusion of nitroxide-labeled lipids in multilamellar liposomal dispersions. Nitroxides with 14N and 15N isotopes introduced both separately and together were used. Differential equations have been written and solved for complex saturation recovery signals involving several superimposed exponentials. The time constants contain various combinations of the spin-lattice relaxation time (T1e) for both isotopes, Heisenberg exchange rates, and nuclear spin-lattice relaxation times (T1n). Signals of high quality were fitted by Monte Carlo variation of the amplitudes and time constants. The reliability of the approach was tested extensively by verifying that (i) the predicted number of exponentials agreed with the experimental number, (ii) relaxation parameters that were determined were independent of the observed hyperfine transition, (iii) the time constants were independent of saturating pu...
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Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites... more
Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated i...
Research Interests: Kinetics, Electron Spin Resonance, Skin Cancer, Reactive Oxygen Species, Methanol, and 12 moreGlutathione, Deuterium, Carcinogens, Superoxide Dismutase, Singlet Oxygen, Poisonous Plants, Spin Trapping, Superoxide Anion, Pyrrolizidine Alkaloids, Superoxides, Solvents, and ENVIRONMENTAL SCIENCE AND MANAGEMENT
Electron spin resonance (ESR) spectroscopy and spin label techniques have been used to study the effects of fumonisin B1 (FB1) and hydrolyzed fumonisin backbone (AP1) on the structural and dynamic properties of phosphatidylcholine... more
Electron spin resonance (ESR) spectroscopy and spin label techniques have been used to study the effects of fumonisin B1 (FB1) and hydrolyzed fumonisin backbone (AP1) on the structural and dynamic properties of phosphatidylcholine membranes at the molecular level. Multilamellar liposomes consisting of dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (EYPC) were used. Six different nitroxide spin labels were used to determine what effects FB1 may impart on the ordering and mobility of lipids in membranes. The experimental results disclose the following: (1) In the fluid phase membrane, FB1 significantly increases the fluidities of n-doxylstearic acid (SA) spin labels (SL) attached to carbons 5 and 7, which disorders the alkyl chains and perturbs the surface region of the bilayer; by comparison, minimal effects were detected near the center of the bilayer. (2) In the gel phase, FB1 and AP1 imparts marked rigidifying effects on membrane fluidity, which enlarges the change in ordering on the phase transition even further. (3) FB1 also restricts the mobility of the (rigid) cholestane spin label. (4) A reduction in mobility of the tempo-stearate spin label suggests that the tricarballylic acid (TCA) moieties of FB1 might mimic the structure of polar headgroups in phospholipids. The present results may provide additional mechanisms to elucidate the toxicological activities of the fumonisins.
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Molecular organization and dynamics in protein-rich membranes have been studied by investigating transport (diffusion-concentration product) of molecular oxygen at various locations in reconstituted membranes of bacteriorhodopsin (BR) and... more
Molecular organization and dynamics in protein-rich membranes have been studied by investigating transport (diffusion-concentration product) of molecular oxygen at various locations in reconstituted membranes of bacteriorhodopsin (BR) and L-alpha-dimyristoylphosphatidylcholine. Oxygen transport was evaluated by monitoring the bimolecular collision of molecular oxygen with four types of nitroxide lipid spin labels placed at various locations in the membrane. The collision rate was estimated from the spin-lattice relaxation times (T1's) measured at various oxygen partial pressures by analyzing the short-pulse saturation recovery ESR signals. CD spectra and decay of polarized flash-induced photodichroism of bacteriorhodopsin indicated that BR molecules are monomers in reconstituted membranes with a lipid/BR molar ratio of 80 (80-rec) and are 25% monomers and 75% trimers plus oligomers of trimers when the lipid/BR ratio is 40 (40-rec). In the 80-rec, the lipid environment is homogeneous on a microsecond scale (T1), probably because the exchange rate of lipids between the bulk and the boundary regions is greater than the T1 relaxation rate (approximately 10(6) s-1). The oxygen collision rate in the hydrophobic region of the 80-rec membrane is smaller by a factor of 1.6 than in that of the lipid membrane without BR, and the effect of BR in decreasing the collision rate is independent of the "depth" in the hydrophobic region. In the 40-rec, two collision rates were observed, one of which is close to those for purple membrane (or the gel-phase membrane), while the other is about the same as was measured in the 80-rec.(ABSTRACT TRUNCATED AT 250 WORDS)
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Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly... more
Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly scavenged by nanoparticles, and lipid peroxidation was inhibited in this study. [Gd@C82(OH)22]n nanoparticles significantly reduced the electron spin resonance (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR spectroscopy. Like-wise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen (1O2) by [Gd@C82(OH)22]n nanoparticles. In vitro studies using liposomes prepared from bovine liver phosphatidylcholine revealed that nanoparticles also had a strong inhibitory effect on lipid peroxidation. Consistent with their ability to scavenge ROS and inhibit lipid peroxidation, we determined that [Gd@C82(OH)22]n nanoparticles also protected cells subject...
Research Interests: Electron Spin Resonance, Oxidative Stress, Mitochondria, Nanotechnology, Molecular Pharmacology, and 24 moreMolecular, Fullerenes, Humans, Reactive Oxygen Species, Mice, Female, Animals, Oxidoreductases, Nanostructures, Rat Brain, Enzyme, Lipid peroxidation, Gadolinium, Endothelial cell, Time Factors, Neoplasms, Singlet Oxygen, In Vitro Studies, Human Disease, Antitumor Activity, Organometallic Compounds, Tumor Growth, Neurosciences, and Adenocarcinoma
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Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1 gene product, can lead to MDR in tumors. However, the physiological role of P-gp in normal tissues is not well understood. Previous studies on multidrug-resistant cells... more
Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1 gene product, can lead to MDR in tumors. However, the physiological role of P-gp in normal tissues is not well understood. Previous studies on multidrug-resistant cells have suggested changes in membrane fluidity and membrane potential associated with P-gp expression, but interpretation of these studies is difficult, because most experimental cells have been selected for long periods in the presence of cytotoxic drugs and may have other host alterations. Therefore, we created two cell lines in which a transfected human MDR1 cDNA is repressed by tetracycline and induced in the absence of tetracycline. One cell line was derived from a mouse embryonic fibroblast cultured from a double (mdr1a/1b) knockout mouse, and the other was from a human HeLa cell line. Analysis of the kinetics of expression of P-gp showed that the mRNA had a half-life of approximately 4 h, and the protein had a half-life of approximately 16 h. P...
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Nano-sized titanium dioxide (TiO(2)) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO(2) nanoparticles (nano-TiO(2)) with different molecular sizes and crystal... more
Nano-sized titanium dioxide (TiO(2)) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO(2) nanoparticles (nano-TiO(2)) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO(2) particles caused phototoxicity, as determined by the MTS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO(2) dose-dependent. The smaller the particle size of the nano-TiO(2) the higher the cell damage. The rutile form of nano-TiO(2) showed less phototoxicity than anatase nano-TiO(2). The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance (ESR) oximetry an...
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Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is currently being clinically tested as a photosensitizer... more
Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is currently being clinically tested as a photosensitizer for PDT. Unfortunately, Pc4 aggregates in aqueous solutions, which dramatically reduces its PDT efficacy and therefore limits its clinical application. We have encapsulated Pc4 using silica nanoparticles (Pc4SNP), which not only improved the aqueous solubility, stability, and delivery of the photodynamic drug but also increased its photodynamic efficacy compared to free Pc4 molecules. Pc4SNP generated photo-induced singlet oxygen more efficiently than free Pc4 as measured by chemical probe and EPR trapping techniques. Transmission electron microscopy and dynamic light scattering measurements showed that the size of the particles is in the range of 25-30 nm. Cell viability measurements demonstrated that Pc4SNP was more phototoxic to A375 or B16-F10 melanoma cells than free Pc4. Pc4SNP photodamaged melanoma cells primarily through apoptosis. Irradiation of A375 cells in the presence of Pc4SNP resulted in a significant increase in intracellular protein-derived peroxides, suggesting a Type II (singlet oxygen) mechanism for phototoxicity. More Pc4SNP than free Pc4 was localized in the mitochondria and lysosomes. Our results show that these stable, monodispersed silica nanoparticles may be an effective new formulation for Pc4 in its preclinical and clinical studies. We expect that modifying the surface of silicon nanoparticles encapsulating the photosensitizers with antibodies specific to melanoma cells will lead to even better early diagnosis and targeted treatment of melanoma in the future.
Research Interests: Flow Cytometry, Nanoparticles, Transmission Electron Microscopy, Apoptosis, Photodynamic Therapy, and 18 moreHumans, Mice, Silica, Melanoma, Animals, Cancer Diagnosis, Dynamic Light Scattering, Cell Viability, Photochemotherapy, Particle Size, Singlet Oxygen, Clinical Study, Organosilicon Compounds, Aqueous Solution, Drug Carriers, Silicon Dioxide, Early Diagnosis, and Clinical Application
Doxorubicin (Dox) is one of the most widely used and successful chemotherapeutic antitumor drugs. Its clinical application is highly limited due to its cumulative dose-related cardiotoxicity. Proposed mechanisms include the generation of... more
Doxorubicin (Dox) is one of the most widely used and successful chemotherapeutic antitumor drugs. Its clinical application is highly limited due to its cumulative dose-related cardiotoxicity. Proposed mechanisms include the generation of reactive oxygen species (ROS)-mediated oxidative stress. Therefore, reducing oxidative stress should be protective against Dox-induced cardiotoxicity. To determine whether antioxidant, grape seed proanthocyanidin extract (GSPE) attenuates Dox-induced ROS generation and protects cardiomyocytes from Dox-induced oxidant injury, cultured primary cardiomyocytes were treated with doxorubicin (Dox, 10 microM) alone or GSPE (50 microg/ml) with Dox (10 microM) for 24 hours. Dox increased intracellular ROS production as measured by 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, induced significant cell death as assessed by propidium iodide, and declined the redox ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and disrupted mitochondrial membrane potential as determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethlbenzimidazole-carbocyanide iodine (JC-1). Analysis of agarose gel electrophoresis revealed Dox-induced nuclear DNA damage with the ladder like fragmentation. GSPE treatment suppressed those alterations. Electron Spin Resonance (ESR) spectroscopy data also showed that GSPE strongly scavenged hydroxyl radical, superoxide and DPPH radicals. Together, these findings indicate that GSPE in combination with Dox has protective effect against Dox-induced toxicity in cardiomyocytes, which may be in part attributed to its antioxidative activity. Importantly, flow cytometric analysis demonstrated that co-treatment of Dox and GSPE did not decrease the proliferation-inhibitory effect of Dox in MCF-7 human breast carcinoma cells. Thus, GSPE may be a promising adjuvant to prevent cardiotoxicity without interfering with antineoplastic activity during chemotherapeutic treatment with Dox.
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To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as... more
To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as an oxidative stress biomarker. These infected mice were pretreated with Ribavirin, ascorbic acid, superoxide dismutase (SOD) or Kegan Liyan oral prescription (KGLY, proprietary Chinese medicine for influenza and common cold) in the stomach tube for 3 days, and then followed by the virus-infecting for 4 days. On the 4th day, samples were collected. It is recognized the strength of ascorbyl radical's ESR signal (A(-.)) (a(H4 = 0.177) Gauss, g = 2.00517) denotes oxidative stress level in vivo and in vitro. The magnitude of ESR spectrum (28.65 +/- 10.71 AU) in mice infected with influenza virus was significantly higher than those of healthy control mice (19.10 +/- 3.61 AU). Serum A(-.) in mice treated with Ribavirin, ascorbic acid, SOD and KGLY declined to 19.70 +/- 6.05, 18.50 +/- 2.93 and 16.25 +/- 3.59, 18.40 +/- 2.14 AU respectively. It is close to A(-.) signal height in healthy controls via down-regulation of the influenza virus-caused oxidative stress level getting decline in the lung index of pneumonia as compare to those of untreated healthy and the influenza virus infected mice pneumonia. It is well known that SOD can prevent the influenza virus pneumonia enhancing mouse survival rate; Ribavirin can treat viral diseases. Data from this study suggested that KGLY may indirectly relieve influenza virus-infected pneumonia via down- regulation of virus caused oxidative stress coupled with a redox reaction cascade as ribavirin, ascorbic acid and SOD.
Research Interests: Free Radicals, Oxidative Stress, Influenza virus, Antioxidants, Phytotherapy, and 16 moreMice, Female, Animals, Male, Lung, Superoxide Dismutase, Ascorbic Acid, Angiosperms, influenza A virus, Biological markers, Oxidation-Reduction, Ribavirin, Antiviral Agents, Orthomyxoviridae Infections, American Chinese Medicine, and Down-Regulation
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... Ramadan, 2007). It is also used as a natural remedy for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and influenza ([Ali and Blunden, 2003] and [Ramadan, 2007]). The ...
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Azulene and guaiazulene are popular ingredients in beauty, cosmetic, skin, and body care products. We previously determined that these chemicals are photomutagenic in Salmonella and phototoxic, causing DNA damage in human Jurkat T-cells.... more
Azulene and guaiazulene are popular ingredients in beauty, cosmetic, skin, and body care products. We previously determined that these chemicals are photomutagenic in Salmonella and phototoxic, causing DNA damage in human Jurkat T-cells. In this study we report that photoirradiation of azulene and guaiazulene, respectively, by UVA light at 0–70J/cm2 in the presence of a lipid, methyl linoleate, resulted in
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A combinative method using high-speed counter-current chromatography (HSCCC) and thin layer chromatography (TLC) as an antioxidant autographic assay was developed to separate antioxidant components from the fruits of Psoralea corylifolia.... more
A combinative method using high-speed counter-current chromatography (HSCCC) and thin layer chromatography (TLC) as an antioxidant autographic assay was developed to separate antioxidant components from the fruits of Psoralea corylifolia. Under the guidance of TLC bioautography, eight compounds including five flavonoids and three coumarins were successfully separated from the fruits of P. corylifolia by HSCCC with an optimized two-phase solvent system, n-hexane-ethyl acetate-methanol-water (1:1.1:1.3:1, v/v/v/v). The separation produced 5.91mg psoralen, 6.26mg isopsoralen, 3.19mg psoralidin, 0.92mg corylifol A, and 2.43mg bavachinin with corresponding purities of 99.5, 99.8, 99.4, 96.4, and 99.0%, as well as three sub-fractions, in a single run from 250mg ethyl acetate fraction of P. corylifolia extract. Following an additional clean-up step by preparative TLC, 0.4mg 8-prenyldaidzein (purity 91.7%), 4.18mg neobavaisoflavone (purity 97.4%) and 4.36mg isobavachalcone (purity 96.8%) were separated from the three individual sub-fractions. The structures of the isolated compounds were identified by (1)H NMR and (13)C NMR. The results of antioxidant activity estimation by electron spin resonance (ESR) method showed that psoralidin was the most active antioxidant with an IC50 value of 44.7microM. This is the first report on simultaneous separation of eight compounds from P. corylifolia by HSCCC.
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Hydroxyl radical scavenging capacity estimation for lipophilic antioxidants is a challenge due to their poor solubility in aqueous radical generating and measuring systems. In this study, an electron spin resonance (ESR) method was... more
Hydroxyl radical scavenging capacity estimation for lipophilic antioxidants is a challenge due to their poor solubility in aqueous radical generating and measuring systems. In this study, an electron spin resonance (ESR) method was developed and validated for its application in estimating the relative hydroxyl radical (HO*) scavenging capacity for lipophilic antioxidants under physiological pH using a Fenton Fe2+/H2O2 system for radical generation and acetonitrile as a solvent. The Fenton Fe2+/H2O2 system generates a constant flux of pure HO* under the assay conditions. The method was validated by linearity, precision, and reproducibility using selected known lipophilic antioxidants including alpha-tocopherol, lutein, beta-carotene, and BHT. The potential effects of commonly used water-miscible and water-immiscible organic solvents on the Fenton Fe2+/H2O2 HO* generating system as well as their possible interactions with the fluorescent and spectroscopic probes were also reported. In addition, the limitation of the ESR assay was described.
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An electron spin resonance (ESR) spectrometry study was conducted to examine the free radical scavenging properties of bran extracts of Alliance and Wichita wheat using hydroxyl radical (HO*), 2,2-diphenyl-1-picryhydrazyl radical (DPPH*),... more
An electron spin resonance (ESR) spectrometry study was conducted to examine the free radical scavenging properties of bran extracts of Alliance and Wichita wheat using hydroxyl radical (HO*), 2,2-diphenyl-1-picryhydrazyl radical (DPPH*), and superoxide radical anion (O2*-) and their chelating capacities against Cu2+. Also reported is the radical cation 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) scavenging activity, oxygen radical absorbing capacity (ORAC), and chelating property against Fe2+ of the bran extracts measured by the spectrophotometric methods. Significant radical scavenging and chelating capacities were detected in the bran extracts, along with significant levels of phenolic acids, tocopherols, and carotenoids. Ferulic acid, with a concentration range of 130.60-146.38 microg/g, was the predominant phenolic acid in all of the tested bran samples and accounted for approximately 53-67% of total phenolic acids on a weight basis. Total tocopherol concentration ranged from 1.87 to 2.95 micromol/100 g of bran, whereas total carotenoid level was 0.20-0.33 micromol/100 g of bran. In addition, both wheat variety and growing conditions might significantly alter antioxidant properties and concentrations of beneficial components in wheat bran.
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Overproduction of reactive oxygen species (ROS) in vivo can result in damage associated with many aging-associated diseases. Defenses against ROS that have evolved include antioxidant enzymes, such as superoxide dismutases, peroxidases,... more
Overproduction of reactive oxygen species (ROS) in vivo can result in damage associated with many aging-associated diseases. Defenses against ROS that have evolved include antioxidant enzymes, such as superoxide dismutases, peroxidases, and catalases, which can scavenge ROS. In addition, endogenous and dietary antioxidants play an important role in moderating damage associated with ROS. In this study, we use four common dietary antioxidants to demonstrate that, in the presence of copper (cupric sulfate and cupric gluconate) and physiologically relevant levels of hydrogen peroxide, these antioxidants can also act as pro-oxidants by producing hydroxyl radicals. Using electron spin resonance (ESR) spin trapping techniques, we demonstrate that the level of hydroxyl radical formation is a function of the pH of the medium and the relative amounts of antioxidant and copper. On the basis of the level of hydroxyl radical formation, the relative pro-oxidant potential of these antioxidants is cysteine > ascorbate > EGCG > GSH. It has been reported that copper sequestered by protein ligands, as happens in vivo, loses its redox activity (diminishing/abolishing the formation of free radicals). However, in the presence of hydrogen peroxide, cysteine and GSH efficiently react with cupric sulfate sequestered with bovine serum albumin to generate hydroxyl radicals. Overall, the results demonstrate that in the presence of copper, endogenous and dietary antioxidants can also exhibit pro-oxidative activity.
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The semiconductor TiO2 is known to have photobiological activity in prokaryotic and eukaryotic cells. Applications of this photobiological activity have been suggested including sterilization of waste water and phototherapy of malignant... more
The semiconductor TiO2 is known to have photobiological activity in prokaryotic and eukaryotic cells. Applications of this photobiological activity have been suggested including sterilization of waste water and phototherapy of malignant cells. Here, several model and cellular systems were used to study the mechanism of photocatalysis by TiO2. Treatment of TiO2 (anatase, 0.45 microns), suspended in water containing a spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), with UV radiation (320 nm) resulted in an electron spin resonance (ESR) signal characteristic of the hydroxyl radical. Irradiation of solutions containing calf thymus DNA and TiO2 with UVA (320-400 nm) radiation resulted in hydroxylation of guanine bases. The degree of hydroxylation was dependent on both UVA fluence and amount of TiO2 in suspension. Human skin fibroblasts, preincubated 18 h with 10 micrograms/cm2 TiO2 and then UVA-irradiated (0-58 KJ/m2), showed dose dependent photocytoxicity. RNA, isolated from similarly treated fibroblasts, contained significant levels of photooxidation, measured as hydroxylation of guanine bases. However, no oxidative damage was detectable in cellular DNA. These results suggest that nucleic acids are a potential target for photooxidative damage sensitized by TiO2, and support the view that TiO2 photocatalyzes free radical formation.
Research Interests: RNA, Photochemistry, Electron Spin Resonance, Titanium, Human Skin Ageing, and 22 moreOxidative Stress, DNA damage, Free Radical, DNA, Cell line, Humans, Animals, Uv Radiation, Titanium dioxide, Skin, Sterilization, Nucleic Acids, RNA isolation, Suspensions, Cattle, Waste Water, Oxidative Damage, Human Fibroblasts, Human skin fibroblasts, Biochemistry and cell biology, Cellular system, and Nucleic Acid
... El Hamss, Idaomar, Alonso-Moraga, & Munoz Serrano, 2003) activity, and might be able to suppress lipid oxidation in animal tissues (Vijayakumar, Surya, & Nalini ... cranberry and hemp seed oils (Yu, Zhou, & Parry, 2005),... more
... El Hamss, Idaomar, Alonso-Moraga, & Munoz Serrano, 2003) activity, and might be able to suppress lipid oxidation in animal tissues (Vijayakumar, Surya, & Nalini ... cranberry and hemp seed oils (Yu, Zhou, & Parry, 2005), and 17.5–19.7 μmol TE/g in wheat bran (Zhou, Su, & Yu ...
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Catechins, which exist in green tea, are excellent antioxidants and metals enhance their pro-oxidative character. In this study, we investigated damage to the cell cytoplasmic membrane of the androgen-insensitive prostate cancer cell PC-3... more
Catechins, which exist in green tea, are excellent antioxidants and metals enhance their pro-oxidative character. In this study, we investigated damage to the cell cytoplasmic membrane of the androgen-insensitive prostate cancer cell PC-3 from rearrangement of EGCG (epigallocatechin gallate), the main bioactive component of catechins. In a cell culture system containing Cu2+, the generation of free radicals from EGCG rearrangement
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Five phenolic acids commonly present in wheat grain and fractions were examined and compared for their radical-scavenging properties and chelating capacities. The free radical-scavenging properties were evaluated against... more
Five phenolic acids commonly present in wheat grain and fractions were examined and compared for their radical-scavenging properties and chelating capacities. The free radical-scavenging properties were evaluated against 2,2-diphenyl-1-picryhydrazyl radical (DPPH), radical cation (ABTS+), peroxide radical anion (O2-) and hydroxyl radical (HO), whereas the chelating properties were evaluated against Fe (II) and Cu (II) using spectrophotometric and electron spin resonance
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The preventive and therapeutic effects of a major component of catechins of green tea, epigallocatechin-3-gallate (EGCG), on prostate cancer have been demonstrated in many studies. It is well known that metal ions are necessary for human... more
The preventive and therapeutic effects of a major component of catechins of green tea, epigallocatechin-3-gallate (EGCG), on prostate cancer have been demonstrated in many studies. It is well known that metal ions are necessary for human health, but an imbalance in metal ions metabolism can lead to many diseases including prostate cancer. Understanding the interactions of EGCG with metal ions might elucidate its mechanism in preventing and curing prostate cancer. The present study focused on the effects of Cd(2+) and EGCG on the growth of androgen-insensitive prostate cancer cell PC-3 investigated by MTT assay, the effects of EGCG and Cd(2+) on absorption of Cd(2+) and Zn(2+) by PC-3 cells were detected by atomic absorption spectroscopy (AAS), and the interactions of EGCG with Cd(2+) were determined by distribution coefficient and UV-Vis spectroscopy detection. The results showed that Cd(2+) suppressed viability of PC-3 cells in concentration- and time-dependent manner, and EGCG enhanced the effect of Cd(2+) on PC-3 cells. EGCG was shown to decrease the absorption Cd(2+) and increase the absorption of Zn(2+) by PC-3 cells, while the effects of Cd(2+) on the absorption of Cd(2+) and Zn(2+) were opposite to that of EGCG. In the presence of both EGCG and Cd(2+), absorption of Cd(2+) and Zn(2+) by PC-3 cells was dependent on concentrations of EGCG, Cd(2+) and its order of addition. Results from the distribution coefficient determination and UV-Vis spectroscopy analysis indicated that Cd(2+) might affect conformation of EGCG, while no complex of EGCG with Cd(2+) was observed in the system.
Research Interests: Drug interactions, Prostate Cancer, Cell Division, Humans, Tea, and 17 moreGreen Tea, Animals, Male, Zinc, Absorption, UV/Vis spectroscopy, Cadmium, Human health, Time Dependent, Time Factors, Food Sciences, Metal ion, Atomic Absorption Spectroscopy, Thiazoles, Food and Chemical Toxicology, Cell Survival, and Catechin
Research Interests: Electron Spin Resonance, Membrane Proteins, Cell Division, Humans, Fatty acids, and 14 moreMembrane Lipids, Clinical Sciences, Cisplatin, Carcinoma, HeLa cells, Neoplasms, Fluorescence polarization, Potassium Channels, Membrane Potential, Plasma Membrane, Fatty Acid Composition, Membrane Fluidity, Biochemistry and cell biology, and Anticancer Drug
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Prostate cancer is threatening human health heavily, for its causes are related to diet, genetic factors, and lifestyle. Metal ions, which are necessary to our health, are important factors inducing many diseases including prostate cancer... more
Prostate cancer is threatening human health heavily, for its causes are related to diet, genetic factors, and lifestyle. Metal ions, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. Epidemiological and laboratory studies provide convincing evidence that green tea prevents and cures prostate cancer. Practically, interactions of catechins, which are the main bioactive components in green tea or GTP, with metal ions have a new aspect to investigate their mechanism in preventing and curing prostate cancer. In the present paper, we summarize some research about the effects of catechins with metal ions related to prostate cancer and their interactions on prostate cancer.
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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous genotoxic environmental pollutants and potentially pose a health risk to humans. In most if not all cases, PAHs in the environment can be oxidized into their corresponding PAH-diones.... more
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous genotoxic environmental pollutants and potentially pose a health risk to humans. In most if not all cases, PAHs in the environment can be oxidized into their corresponding PAH-diones. This process is considered a detoxification pathway with regard to tumorigenicity. Nevertheless, photo-induced toxicological activity of PAH-diones has not been systematically investigated. In this study, we show that 27 potential environmental PAH-diones induced lipid peroxidation, in a dose (light) response manner, when irradiated with UVA at 7 and 21 J cm(-2). Photoirradiation in the presence of sodium azide, deuterated methanol, or superoxide dismutase revealed that lipid peroxidation is mediated by reactive oxygen species. Electron spin resonance (ESR) spin trapping studies supported this observation. These results suggest that UVA photoirradiation of PAH-diones generates reactive oxygen species and induces lipid peroxidation.
Research Interests: Free Radicals, Electron Spin Resonance, Multidisciplinary, Reactive Oxygen Species, Detoxification, and 9 morePolycyclic Aromatic Hydrocarbon, Superoxide Dismutase, Lipid peroxidation, Polycyclic aromatic hydrocarbons (PAHs), Singlet Oxygen, Health risk, Mutagens, Superoxides, and Photochemical Processes
The water-soluble fullerene derivative gamma-cyclodextrin bicapped C(60) [(gamma-CyD)(2)/C(60), CDF0] has several clinical applications, including use as a drug carrier to bypass the blood ocular barriers or a photosensitizer to treat... more
The water-soluble fullerene derivative gamma-cyclodextrin bicapped C(60) [(gamma-CyD)(2)/C(60), CDF0] has several clinical applications, including use as a drug carrier to bypass the blood ocular barriers or a photosensitizer to treat tumors in photodynamic therapy. We have assessed the potential ocular toxicity of (gamma-CyD)(2)/C(60) and its aggregated derivatives induced by UVA and visible light in vitro in human lens epithelial cells (HLE B-3). Cell viability using the MTS assay demonstrated that 2 microM (gamma-CyD)(2)/C(60) was highly phototoxic to HLE B-3 cells with UVA irradiation, while no effect was observed in the presence of visible light or when maintained in the dark. In contrast, the aggregated derivative (CDF150) showed neither cytotoxicity nor any phototoxic effect even at 30 microM with either UVA or visible light irradiation. In lens cells treated with (gamma-CyD)(2)/C(60), phototoxicity was manifested as apoptosis. Singlet oxygen production measurement using the EPR/TEMP trapping technique determined that (gamma-CyD)(2)/C(60) (CDF0) efficiently produced singlet oxygen. The rate of singlet oxygen production decreased with increased aggregation, with no production by the fully aggregated sample formed after 150 min of heating (CDF150). UVA irradiation of HLE B-3 in the presence of (gamma-CyD)(2)/C(60) resulted in a significant rise in intracellular protein-derived peroxides. The singlet oxygen quenchers sodium azide and histidine each significantly protected lens cells against (gamma-CyD)(2)/C(60) photodamage, but lutein and Trolox (vitamin E) did not. Clearly, singlet oxygen is an important intermediate in the phototoxicity of monomeric (gamma-CyD)(2)/fullerene. Our results also demonstrate that UVA-blocking sunglasses can limit the ocular phototoxicity of this nanomaterial, while nontoxic endogenous antioxidants like lutein or Trolox cannot provide adequate protection.
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Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of... more
Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification. We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 microM). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells. Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells.
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Research Interests: Oxidative Stress, Herbal Medicine, Antioxidants, Animals, Male, and 16 moreCancer Chemotherapy, Food intake, Panax, Cisplatin, Plant extracts, Dose Response Relationship, Rats, Body Weight, Wistar Rats, In Vitro Studies, Pica, Kaolin, Antineoplastic Agents, Vomiting, Antioxidant Capacity, and Ginsenosides
A pulse saturation-recovery electron paramagnetic resonance (EPR) method has been developed that allows estimation of the exchange rates of a spin-labeled lipid between the bulk domain and the protein-rich membrane domain, in which the... more
A pulse saturation-recovery electron paramagnetic resonance (EPR) method has been developed that allows estimation of the exchange rates of a spin-labeled lipid between the bulk domain and the protein-rich membrane domain, in which the rate of collision between the spin label and molecular oxygen is reduced (slow-oxygen transport domain, or SLOT domain). It is based on the measurements of saturation-recovery signals of a lipid spin label as a function of concentrations of both molecular oxygen and the spin label. Influenza viral membrane, one of the simplest paradigms for the study of biomembranes, showed the presence of two membrane domains with slow and fast collision rates with oxygen (a 16-fold difference) at 30 degrees C. The outbound rate from and the inbound rate into the SLOT domain (or possibly the rate of the domain disintegration and formation) were estimated to be 7.7 x 10(4) and 4.6 x 10(4) s(-1), (15 micros residency time), respectively, indicating that the SLOT domain is highly dynamic and that the entire SLOT domain represents about one-third of the membrane area. Because the oxygen transport rate in the SLOT domain is a factor of two smaller than that in purple membrane, where bacteriorhodopsin is aggregated, we propose that the SLOT domain in the viral membrane is the cholesterol-rich raft domain stabilized by the trimers of hemagglutinin and/or the tetramers of neuraminidase.
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Electron spin resonance (ESR) spin-label oximetry has been used to study the effects of fumonisin B1 (FB1), a sphingoid-like mycotoxin, on oxygen transport in phosphatidylcholine (PC) bilayers. Moreover, the use of spin labels attached to... more
Electron spin resonance (ESR) spin-label oximetry has been used to study the effects of fumonisin B1 (FB1), a sphingoid-like mycotoxin, on oxygen transport in phosphatidylcholine (PC) bilayers. Moreover, the use of spin labels attached to different carbons of fatty acids makes it possible to do structural and oximetric determinations with the same test sample. Specifically, the incorporation of 10 mol% FB1 increased the oxygen transport properties of both saturated and unsaturated membranes at 37 degrees C by ca. 30% and decreased the ordering of the hydrocarbon chains near the surface of the membranes; concomitantly, oxygen transport near the center of bilayers was diminished slightly, and the relative oxygen diffusion-concentration product profile curves were markedly flattened.
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Electron spin resonance (ESR)1 spin-label oximetry and spin trapping techniques have been used to study the effect of fumonisin B1 (FB1), an amphipathic mycotoxin on lipid peroxidation in egg yolk phosphatidylcholine (EYPC) bilayers. In... more
Electron spin resonance (ESR)1 spin-label oximetry and spin trapping techniques have been used to study the effect of fumonisin B1 (FB1), an amphipathic mycotoxin on lipid peroxidation in egg yolk phosphatidylcholine (EYPC) bilayers. In the study of the interaction between FB1 and lipid bilayers our results show that fumonisin disturbs the ordering of membranes, enhances oxygen transport in membranes, and also increases membrane permeability. In our model system, lipid peroxidations were initiated by extended incubation of the liposomes, or by inducing Fe2+ ions, UV illumination of H2O2 or ultrasound irradiation. As an indication of the rates of lipid oxidation in EYPC, the consumption of molecular oxygen was studied by monitoring the oxygen concentration in the aqueous phases of the liposomes. Lipid-derived free radicals generated during the oxidation process were measured by a spin trapping method. The incorporation of FB1 in the test samples made the membranes highly susceptible to oxidation. Our results provide the first evidence that the fumonisins appear to increase the rate of oxidation, promote the free radical intermediate production and accelerate the chain reactions associated with lipid peroxidation. The disruption of membrane structure, the enlargement of the relative oxygen diffusion-concentration products, as well as the enhancement effects on membrane permeability, thus provide additional insights into potential mechanisms by which the fumonisins could enhance oxidative stress and cell damage.
Research Interests: Chemical Engineering, Electron Spin Resonance, Ultrasound, Free Radical, Biological Sciences, and 16 moreMycotoxins, Physical sciences, Ultrasonics, Liposomes, Iron, Lipid Oxidation, Lipid peroxidation, Hydrogen Peroxide, Oxygen Transport, Model System, Carboxylic Acids, Spin Trapping, Lipid Bilayer, Oxygen Consumption, Fumonisins, and Biochemistry and cell biology
Electron spin resonance (ESR) spectroscopy and spin label techniques have been used to study the effects of fumonisin B1 (FB1) and hydrolyzed fumonisin backbone (AP1) on the structural and dynamic properties of phosphatidylcholine... more
Electron spin resonance (ESR) spectroscopy and spin label techniques have been used to study the effects of fumonisin B1 (FB1) and hydrolyzed fumonisin backbone (AP1) on the structural and dynamic properties of phosphatidylcholine membranes at the molecular level. Multilamellar liposomes consisting of dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (EYPC) were used. Six different nitroxide spin labels were used to determine what effects FB1 may impart on the ordering and mobility of lipids in membranes. The experimental results disclose the following: (1) In the fluid phase membrane, FB1 significantly increases the fluidities of n-doxylstearic acid (SA) spin labels (SL) attached to carbons 5 and 7, which disorders the alkyl chains and perturbs the surface region of the bilayer; by comparison, minimal effects were detected near the center of the bilayer. (2) In the gel phase, FB1 and AP1 imparts marked rigidifying effects on membrane fluidity, which enlarges the change in ordering on the phase transition even further. (3) FB1 also restricts the mobility of the (rigid) cholestane spin label. (4) A reduction in mobility of the tempo-stearate spin label suggests that the tricarballylic acid (TCA) moieties of FB1 might mimic the structure of polar headgroups in phospholipids. The present results may provide additional mechanisms to elucidate the toxicological activities of the fumonisins.