Influence of vitamin E succinate on retinal cell survival.
In this study, we analyzed the influence of vitamin E succinate (5-80 microM), supplemented in the culture medium, on the survival of cultured retinal cells. The release of lactate dehydrogenase (LDH) was decreased in the presence of low concentrations (10-20 microM) of vitamin E succinate, whereas high concentrations (80 microM) induced a significant increase (about 2-fold) in the release of LDH, indicating a reduction of plasma membrane integrity. Supplementing with vitamin E succinate (80 microM) greatly enhanced its cellular content, as compared to vitamin E acetate (80 microM), and the membrane order of the retinal cells, as evaluated by the fluorescence anisotropy (r) of TMA-DPH (1-(4-(trimethylammonium)-phenyl)-6-phenylhexa-1,3,5-triene), was not altered. Furthermore, vitamin E succinate was more potent than vitamin E acetate in reducing thiobarbituric acid reactive substances (TBARS) formation upon ascorbate-Fe2+-induced oxidative stress (TBARS formation after cell oxidation decreased by about 15-fold or 1.6 fold, respectively, in the presence of 20 microM vitamin E succinate or 20 microM vitamin E acetate). A decrease in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction induced by supplementing with vitamin E succinate (80 microM), to 35.99 +/- 1.96% as compared to the control, but not by vitamin E acetate (80 microM), suggests that vitamin E succinate may affect the mitochondrial activity. Vitamin E succinate also reduced significantly the ATP:ADP ratio in a dose-dependent manner, indicating that vitamin E succinate-mediated cytotoxic effects involve a decrement of mitochondrial function.
Center for Neurosciences of Coimbra, Faculty of Medicine, University of Coimbra, Portugal.
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D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003470:Culture Media; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D005980:Glutathione Reductase / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D012160:Retina / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D000975:Antioxidants; D003470:Culture Media; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D004161:Diphenylhexatriene; D000244:Adenosine Diphosphate; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; C022616:thiazolyl blue; D024502:alpha-Tocopherol; D024505:Tocopherols