title: Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid.
abstract: Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant of retinal membranes whose deficiency causes retinal degeneration. Its antioxidant function is realized via scavenging peroxyl radicals as a result of which phenoxyl radicals of alpha-tocopherol are formed. Our hypothesis is that alpha-tocopherol phenoxyl radicals can be reduced by endogenous reductants in the retina, providing for alpha-tocopherol recycling. The results of this study demonstrate for the first time that: (i) endogenous ascorbate (vitamin C) in retinal homogenates and in rod outer segments is able to protect endogenous alpha-tocopherol against oxidation induced by UV-irradiation by reducing the phenoxyl radical of alpha-tocopherol, (ii) in the absence of ascorbate, neither endogenous nor exogenously added glutathione (GSH) is efficient in protecting alpha-tocopherol against oxidation; (iii) GSH does not substantially enhance the protective effect of ascorbate against alpha-tocopherol oxidation; (iv) exogenous dihydrolipoic acid (DHLA), although inefficient in direct reduction of the alpha-tocopherol phenoxyl radical, is able to enhance the protective effect of ascorbate by regenerating it from dehydroascorbate. Thus, regeneration of alpha-tocopherol from its phenoxyl radical can enhance its antioxidant effectiveness in the retina. The recycling of alpha-tocopherol opens new avenues for pharmacological approaches to enhance antioxidants of the retina.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Stoyanovsky
authors.forename: R
authors.initials: R
authors.lastname: Goldman
authors.forename: R M
authors.initials: RM
authors.lastname: Darrow
authors.forename: D T
authors.initials: DT
authors.lastname: Organisciak
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000096:biosynthesis*
chemical_list: D005609:Free Radicals; D014810:Vitamin E; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid