Enhanced antioxidant and cytoprotective abilities of vitamin E succinate is associated with a rapid uptake advantage in rat hepatocytes and mitochondria.
Numerous in vitro studies attest to the enhanced ability of vitamin E succinate (TS), as compared with conventional vitamin E compounds such as unesterified d-alpha-tocopherol (T) and d-alpha-tocopheryl acetate (TA), to protect hepatocytes from toxic oxidative stress. In the present study we tested the hypothesis that this unique protective ability is related to an enhanced cellular accumulation of TS. The results of this study indicate, using both in vitro and in vivo model systems, that acute TS administration results in a rapid increase in T and TS content and antioxidant protection of hepatocytes and mitochondria. In contrast, conventional vitamin E compounds such as T and TA lack these same protective properties. We suggest that TS acts as a unique delivery system for T, rapidly accumulating in cellular and mitochondrial membranes and gradually releasing active T to prevent membrane oxidative damage. We propose that TS administration may prove useful for the prevention and treatment of oxidative stress-mediated diseases, especially those of mitochondrial origin.
Fariss
M W
MW
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA. fariss@wsu.edu
Nicholls-Grzemski
F A
FA
Tirmenstein
M A
MA
Zhang
J G
JG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D005609:Free Radicals; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D024505:Tocopherols