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Cell Biochemistry and Biophysics Jun 2020Iron-catalyzed, free radical-mediated lipid peroxidation may play a major role in tumor cell killing by photodynamic therapy (PDT), particularly when membrane-localizing... (Review)
Review
Iron-catalyzed, free radical-mediated lipid peroxidation may play a major role in tumor cell killing by photodynamic therapy (PDT), particularly when membrane-localizing photosensitizers are employed. Many cancer cells exploit endogenous iNOS-generated NO for pro-survival/expansion purposes and for hyper-resistance to therapeutic modalities, including PDT. In addition to inhibiting the pro-oxidant activity of Fe(II) via nitrosylation, NO may intercept downstream lipid oxyl and peroxyl radicals, thereby acting as a chain-breaking antioxidant. We investigated this for the first time in the context of PDT by using POPC/Ch/PpIX (100:80:0.2 by mol) liposomes (LUVs) as a model system. Cholesterol (Ch or [C]Ch) served as an in-situ peroxidation probe and protoporphyrin IX (PpIX) as photosensitizer. PpIX-sensitized lipid peroxidation was monitored by two analytical methods that we developed: HPLC-EC(Hg) and HPTLC-PI. 5α-hydroperoxy-Ch (5α-OOH) accumulated rapidly and linearly with irradiation time, indicating singlet oxygen (O) intermediacy. When ascorbate (AH) and trace lipophilic iron [Fe(HQ)] were included, 7α/7β-hydroperoxy-Ch (7-OOH) accumulated exponentially, indicating progressively greater membrane-damaging chain lipid peroxidation. With AH/Fe(HQ) present, the NO donor SPNO had no effect on 5α-OOH formation, but dose-dependently inhibited 7-OOH formation due to NO interception of chain-carrying oxyl and peroxyl radicals. Similar results were obtained when cancer cells were PpIX/light-treated, using SPNO or activated macrophages as the NO source. These findings implicate chain lipid peroxidation in PDT-induced cytotoxicity and NO as a potent antagonist thereof by acting as a chain-breaking antioxidant. Thus, unless NO formation in aggressive tumors is suppressed, it can clearly compromise PDT efficacy.
Topics: Animals; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Free Radicals; Humans; Hydrogen Peroxide; Lipid Peroxidation; Lipids; Liposomes; Macrophages; Neoplasms; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidants; Oxidative Stress; Peroxides; Photochemotherapy; Photosensitizing Agents
PubMed: 32303898
DOI: 10.1007/s12013-020-00909-2 -
Pigment Cell & Melanoma Research Jul 2018RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, is known to induce leukoderma in some consumers. To explore the mechanism underlying this...
RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, is known to induce leukoderma in some consumers. To explore the mechanism underlying this effect, we previously showed that the oxidation of RD with mushroom or human tyrosinase produces cytotoxic quinone oxidation products and RD-eumelanin exerts a potent pro-oxidant activity. Cellular antioxidants were oxidized by RD-eumelanin with a concomitant production of H O . In this study, we examined whether this pro-oxidant activity of RD-eumelanin is enhanced by ultraviolet A (UVA) radiation because most RD-induced leukoderma lesions are found in sun-exposed areas. Exposure to a physiological level of UVA (3.5 mW/cm ) induced a two to fourfold increase in the rates of oxidation of GSH, cysteine, ascorbic acid, and NADH. This oxidation was oxygen-dependent and was accompanied by the production of H O . These results suggest that RD-eumelanin is cytotoxic to melanocytes through its potent pro-oxidant activity that is enhanced by UVA radiation.
Topics: Butanols; Hydrogen Peroxide; Melanins; Oxidants; Oxidation-Reduction; Ultraviolet Rays
PubMed: 29474003
DOI: 10.1111/pcmr.12696 -
Talanta Apr 2022Frequent use of persulfates as oxidants, for in situ chemical oxidation and advanced oxidation processes, warrants the need for developing a fast and efficient method...
Frequent use of persulfates as oxidants, for in situ chemical oxidation and advanced oxidation processes, warrants the need for developing a fast and efficient method for measuring persulfate concentrations in aqueous samples in the lab and on site. Here, we propose a modified method, based on Liang et al.'s (2008) spectrophotometric method, for measuring both peroxydisulfate (PDS) and peroxymonosulfate (PMS) in the aqueous samples. Our method involves a deep 96-well plate, multi-channel pipettes, a small orbital shaker, and a microplate reader; allowing the preparation and analysis of up to 96 samples in one run. Our proposed method shortens the time by 10 folds, consumes only ∼2% of the original reagents, and generates only ∼2% of the liquid waste compared to the Liang et al.'s method, thus, making our method high-throughput, time-efficient, and cost-effective with reduced environmental impact. The presented microplate reader method is validated in terms of linearity, LOD, LOQ, accuracy, precision, robustness, and selectivity. All the parameters satisfied the acceptance criteria, according to ICH guidelines. The linearity of calibration curves was evaluated by performing the F-test. In general, our method has linear ranges from 20 to 42,000 and 5 to 40,960 μM for PDS and PMS, respectively. Accuracy (% recovery) results suggested that the LOD and LOQ based on the standard deviation of y-intercepts of the regression lines were the most reliable. The LOD/LOQ values for PDS and PMS were 14.7/44.1 and 4.6/14.4 μM, respectively. The proposed method was also modified to work with a standard cuvette spectrophotometer and was validated. A comparison with the UHPLC analysis of PDS showed that our microplate reader method performed equivalently or even outperformed the UHPLC method, in the presence of common groundwater constituents and organic contaminants.
Topics: Cost-Benefit Analysis; Groundwater; Oxidants; Peroxides
PubMed: 35007773
DOI: 10.1016/j.talanta.2021.123170 -
Nature May 2024Cytochrome P450 enzymes are known to catalyse bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and...
Cytochrome P450 enzymes are known to catalyse bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and desaturation. Developing analogous catalytic systems for remote C-H functionalization remains a significant challenge. Here, we report the development of Cu(I)-catalysed bimodal dehydrogenation/lactonization reactions of synthetically common N-methoxyamides through radical abstractions of the γ-aliphatic C-H bonds. The feasibility of switching from dehydrogenation to lactonization is also demonstrated by altering reaction conditions. The use of a readily available amide as both radical precursor and internal oxidant allows for the development of redox-neutral C-H functionalization reactions with methanol as the sole side product. These C-H functionalization reactions using a Cu(I) catalyst with loading as low as 0.5 mol.% is applied to the diversification of a wide range of aliphatic acids including drug molecules and natural products. The exceptional compatibility of this catalytic system with a wide range of oxidatively sensitive functionality demonstrates the unique advantage of using a simple amide substrate as a mild internal oxidant.
Topics: Amides; Carbon; Catalysis; Copper; Cytochrome P-450 Enzyme System; Hydrogen; Hydrogenation; Lactones; Methanol; Oxidants; Oxidation-Reduction
PubMed: 38547926
DOI: 10.1038/s41586-024-07341-z -
Journal of the American Chemical Society Dec 2023The practical catalytic enantioselective -dihydroxylation of olefins that utilize earth-abundant first-row transition metal catalysts under environmentally friendly...
The practical catalytic enantioselective -dihydroxylation of olefins that utilize earth-abundant first-row transition metal catalysts under environmentally friendly conditions is an important yet challenging task. Inspired by the -dihydroxylation reactions catalyzed by Rieske dioxygenases and non-heme iron models, we report the biologically inspired -dihydroxylation catalysis that employs an inexpensive and readily available mononuclear non-heme manganese complex bearing a tetradentate nitrogen-donor ligand and aqueous hydrogen peroxide (HO) and potassium peroxymonosulfate (KHSO) as terminal oxidants. A wide range of olefins are efficiently oxidized to enantioenriched -diols in practically useful yields with excellent -dihydroxylation selectivity and enantioselectivity (up to 99% ee). Mechanistic studies, such as isotopically O-labeled water experiments, and density functional theory (DFT) calculations support that a manganese(V)-oxo-hydroxo (HO-Mn═O) species, which is formed via the water-assisted heterolytic O-O bond cleavage of putative manganese(III)-hydroperoxide and manganese(III)-peroxysulfate precursors, is the active oxidant that effects the -dihydroxylation of olefins; this is reminiscent of the frequently postulated iron(V)-oxo-hydroxo (HO-Fe═O) species in the catalytic arene and alkene -dihydroxylation reactions by Rieske dioxygenases and synthetic non-heme iron models. Further, DFT calculations for the mechanism of the HO-Mn═O-mediated enantioselective -dihydroxylation of olefins reveal that the first oxo attack step controls the enantioselectivity, which exhibits a high preference for -dihydroxylation over epoxidation. In this study, we are able to replicate both the catalytic function and the key chemical principles of Rieske dioxygenases in mononuclear non-heme manganese-catalyzed enantioselective -dihydroxylation of olefins.
Topics: Dioxygenases; Hydrogen Peroxide; Manganese; Oxidation-Reduction; Alkenes; Stereoisomerism; Iron; Oxidants; Catalysis; Water
PubMed: 38064642
DOI: 10.1021/jacs.3c09508 -
Journal of Contaminant Hydrology Aug 2016In situ chemical oxidation (ISCO) has become a widely used technology for the remediation of soil and groundwater. Although peroxymonosulfate is not a common oxidant...
In situ chemical oxidation (ISCO) has become a widely used technology for the remediation of soil and groundwater. Although peroxymonosulfate is not a common oxidant source for ISCO, its chemical structure is similar to the ISCO reagents hydrogen peroxide and persulfate, suggesting that peroxymonosulfate may have the beneficial properties of each of these oxidants. Peroxymonosulfate activation in the presence of subsurface minerals was examined as a basis for ISCO, and possible reactive species (hydroxyl radical, sulfate radical, and reductants+nucleophiles) generated in the mineral-activated peroxymonosulfate systems were investigated. Rates of peroxymonosulfate decomposition and generation rates of reactive species were studied in the presence of three iron oxides, one manganese oxide, and three soil fractions. The iron oxide hematite-activated peroxymonosulfate system most effectively degraded the hydroxyl radical probe nitrobenzene. Reductants+nucleophiles were not generated in mineral-activated peroxymonosulfate systems. Use of the probe compound anisole in conjunction with scavengers demonstrated that both sulfate radical and hydroxyl radical are generated in mineral-activated peroxymonosulfate systems. In order to confirm the activation of peroxymonosulfate by subsurface minerals, one natural soil and associated two soil fractions were evaluated as peroxymonosulfate catalysts. The natural soil did not effectively promote the generation of oxidants; however, the soil organic matter was found to promote the generation of reductants + nucleophiles. The results of this research show that peroxymonosulfate has potential as an oxidant source for ISCO applications, and would be most effective in treating halogenated contaminants when soil organic matter is present in the subsurface.
Topics: Anisoles; Ferric Compounds; Hydrogen-Ion Concentration; Hydroxyl Radical; Manganese Compounds; Minerals; Oxidants; Oxidation-Reduction; Oxides; Peroxides; Reducing Agents; Soil; Soil Pollutants; Sulfates
PubMed: 27209171
DOI: 10.1016/j.jconhyd.2016.05.001 -
Redox Biology Aug 2016Lipid oxidation has been implicated in the pathogenesis of many diseases. Lipids are oxidized in vivo by several different oxidants to give diverse products, in general...
Plasma lipid oxidation induced by peroxynitrite, hypochlorite, lipoxygenase and peroxyl radicals and its inhibition by antioxidants as assessed by diphenyl-1-pyrenylphosphine.
Lipid oxidation has been implicated in the pathogenesis of many diseases. Lipids are oxidized in vivo by several different oxidants to give diverse products, in general lipid hydroperoxides as the major primary product. In the present study, the production of lipid hydroperoxides in the oxidation of mouse plasma induced by multiple oxidants was measured using diphenyl-1-pyrenylphosphine (DPPP) as a probe. DPPP itself is not fluorescent, but it reacts with lipid hydroperoxides stochiometrically to give highly fluorescent DPPP oxide and lipid hydroxides. The production of lipid hydroperoxides could be followed continuously in the oxidation of plasma induced by peroxynitrite, hypochlorite, 15-lipoxygenase, and peroxyl radicals with a microplate reader. A clear lag phase was observed in the plasma oxidation mediated by aqueous peroxyl radicals and peroxynitrite, but not in the oxidation induced by hypochlorite and lipoxygenase. The effects of several antioxidants against lipid oxidation induced by the above oxidants were assessed. The efficacy of antioxidants was dependent markedly on the type of oxidants. α-Tocopherol exerted potent antioxidant effects against peroxyl radical-mediated lipid peroxidation, but it did not inhibit lipid oxidation induced by peroxynitrite, hypochlorite, and 15-lipoxygenase efficiently, suggesting that multiple antioxidants with different selectivities are required for the inhibition of plasma lipid oxidation in vivo. This is a novel, simple and most high throughput method to follow plasma lipid oxidation induced by different oxidants and also to assess the antioxidant effects in biologically relevant settings.
Topics: Animals; Antioxidants; Biomarkers; Hypochlorous Acid; Lipid Peroxidation; Lipids; Lipoxygenase; Male; Mice; Organophosphorus Compounds; Oxidants; Oxidation-Reduction; Peroxides; Peroxynitrous Acid; Pyrenes
PubMed: 26774081
DOI: 10.1016/j.redox.2016.01.005 -
Ecotoxicology and Environmental Safety Jan 2023Experiments for simultaneous elimination and detoxification of microgram level of As(Ⅲ) in the presence of micromolar HO and Fe(Ⅱ) which are frequently encountered...
Experiments for simultaneous elimination and detoxification of microgram level of As(Ⅲ) in the presence of micromolar HO and Fe(Ⅱ) which are frequently encountered in natural water were conducted. The results showed that the molar ratio of oxidant to As(III) plays important role in As(III) oxidation under the experimental conditions. The extent of As(Ⅲ) oxidation with single HO or Fe(Ⅱ) ranged from 7.9 % to 60.3 % and 22.2-46.6 %, respectively. Treatments with HOAs(Ⅲ) molar ratios in the range 150: 1-750: 1 or Fe(Ⅱ)/As(Ⅲ) molar ratios in the range 37.5: 1-375: 1 were more favor for As(Ⅲ) oxidation respectively, and increasing oxidant concentration did not result in complete As(Ⅲ) oxidation. As(Ⅲ) was completely oxidized and eliminated following the precipitation of ferric hydroxides in 5 reaction minutes when HO and Fe(Ⅱ) coexisted in the reaction system. The interface characterization for the reacted precipitates after the experiment were conducted by using a high-resolution field emission scanning electron microscopy (SEM) coupled with an EX-350 energy dispersive X-ray spectrometer (EDX) and X-ray photoelectron spectroscopy (XPS), respectively. The results showed that As(Ⅴ) was the merely arsenic species and As oxide primary situated in the subsurface layer of the reacted precipitates, whereas Fe was more concentrated in the outermost surface layer. Our research showed that HO and Fe(Ⅱ) at natural level may exert significant influence on arsenic mobilization in natural water. Considering the much more toxic of As(Ⅲ) than that of As(Ⅴ), the research also provide us an environmental friendly choice in the elimination and detoxification of microgram As(Ⅲ) in drinking water.
Topics: Hydrogen Peroxide; Arsenic; Arsenites; Ferric Compounds; Oxidation-Reduction; Oxidants; Water; Water Pollutants, Chemical; Ferrous Compounds
PubMed: 38321657
DOI: 10.1016/j.ecoenv.2022.114435 -
Free Radical Biology & Medicine Jun 2015
Topics: Humans; Hydrogen Peroxide; Oxidants; Oxidation-Reduction; Protein Folding; Proteins
PubMed: 25999290
DOI: 10.1016/j.freeradbiomed.2015.05.001 -
PLoS Genetics Feb 2024Misfolded proteins are usually refolded to their functional conformations or degraded by quality control mechanisms. When misfolded proteins evade quality control, they...
Misfolded proteins are usually refolded to their functional conformations or degraded by quality control mechanisms. When misfolded proteins evade quality control, they can be sequestered to specific sites within cells to prevent the potential dysfunction and toxicity that arises from protein aggregation. Btn2 and Hsp42 are compartment-specific sequestrases that play key roles in the assembly of these deposition sites. Their exact intracellular functions and substrates are not well defined, particularly since heat stress sensitivity is not observed in deletion mutants. We show here that Btn2 and Hsp42 are required for tolerance to oxidative stress conditions induced by exposure to hydrogen peroxide. Btn2 and Hsp42 act to sequester oxidized proteins into defined PQC sites following ROS exposure and their absence leads to an accumulation of protein aggregates. The toxicity of protein aggregate accumulation causes oxidant sensitivity in btn2 hsp42 sequestrase mutants since overexpression of the Hsp104 disaggregase rescues oxidant tolerance. We have identified the Sup35 translation termination factor as an in vivo sequestrase substrate and show that Btn2 and Hsp42 act to suppress oxidant-induced formation of the yeast [PSI+] prion, which is the amyloid form of Sup35. [PSI+] prion formation in sequestrase mutants does not require IPOD (insoluble protein deposit) localization which is the site where amyloids are thought to undergo fragmentation and seeding to propagate their heritable prion form. Instead, both amorphous and amyloid Sup35 aggregates are increased in btn2 hsp42 mutants consistent with the idea that prion formation occurs at multiple intracellular sites during oxidative stress conditions in the absence of sequestrase activity. Taken together, our data identify protein sequestration as a key antioxidant defence mechanism that functions to mitigate the damaging consequences of protein oxidation-induced aggregation.
Topics: Protein Aggregates; Prions; Saccharomyces cerevisiae Proteins; Molecular Chaperones; Saccharomyces cerevisiae; Oxidative Stress; Amyloid; Oxidants; Peptide Termination Factors
PubMed: 38422160
DOI: 10.1371/journal.pgen.1011194