Alpha-tocopheryl succinate protects hepatocytes from chemical-induced toxicity under physiological calcium conditions.
Rat and canine hepatocyte suspensions were exposed to toxic concentrations of ethyl methanesulfonate (EMS) and ionophore A-23187 in the presence and absence of extracellular calcium (Ca2+) and alpha-tocopheryl succinate (alpha-TS). The exogenous administration of alpha-TS (25 microM) completely protected hepatocytes from chemically-induced toxicity when exposed to 'physiological' free extracellular calcium concentrations (0.8-1.5 mM). Under these protective conditions the cellular accumulation of both alpha-TS (2.8 nmol/10(6) cells) and alpha-T (0.91 nmol/10(6) cells) were observed. Hepatocytes exposed to unesterified alpha-tocopherol (alpha-T, 25 microM) or alpha-tocopheryl acetate (alpha-TA, 25 microM), however, were not protected from the toxic effect of chemicals even though these treatments resulted in the marked accumulation of cellular alpha-T (2.65 nmol/10(6) cells) and alpha-TA (2.3 nmol/10(6) cells), respectively. Our findings suggest that the supplementation of endogenous stores of alpha-T or alpha-TA does not promote protection against chemical toxicity and that alpha-TS cytoprotection results not from the accumulation of alpha-T but rather from the cellular presence of the intact alpha-TS molecule. Thus alpha-TS appears to possess cytoprotective properties that differ from other vitamin E congeners.
Fariss
M W
MW
Department of Pathology, Virginia Commonwealth University, Richmond 23298-0662.
Merson
M H
MH
O'Hara
T M
TM
D000818:Animals; D000001:Calcimycin / Q000633:toxicity*; D002118:Calcium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D004347:Drug Interactions; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D008054:Lipid Peroxides; D014810:Vitamin E; D000001:Calcimycin; D005020:Ethyl Methanesulfonate; D007770:L-Lactate Dehydrogenase; D024505:Tocopherols; D011188:Potassium; D002118:Calcium