title: Dietary antioxidants provide differential subcellular protection in epithelial cells.
abstract: This study aimed to evaluate the organelle-specific antioxidant/pro-oxidant actions of clinically important dietary antioxidants against oxidative stress. An in vitro cellular model was employed to investigate the antioxidant/pro-oxidant effects of various concentrations (1, 10 and 100 microM) of ascorbic acid, alpha-tocopherol and beta-carotene during H2O2-induced oxidative stress. Damage to nuclear and mitochondrial genomes was analyzed by quantitative polymerase chain reaction and oxidation of membrane lipids was measured via colorimetric assays. The key findings were: (i) dietary antioxidants conferred a dose-dependent protective effect (with a pro-oxidant shift at higher concentrations); (ii) the protection conferred to different sub-cellular organelles is highly specific to the dietary antioxidant; (iii) the mtDNA is highly sensitive to oxidative attack compared to nDNA (P < 0.05); and (iv) mtDNA protection conferred by dietary antioxidants was required to improve protection against oxidative-induced cell death. This study shows that antioxidant-induced protection of mtDNA is an important target for future oxidative stress therapies.
authors.affiliation: Cell and Molecular Biology Unit, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Jarrett
authors.forename: Joy
authors.initials: J
authors.lastname: Cuenco
authors.forename: Mike
authors.initials: M
authors.lastname: Boulton
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D019207:beta Carotene; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D001205:Ascorbic Acid