α-tocopheryl succinate protects hepatocytes from chemical-induced toxicity under physiological calcium conditions

Abstract

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 (Ca 2+) and α-tocopheryl succinate (α-TS). The exogenous administration of α-TS (25 μM) 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 α-TS (2.8 nmol/10 6 cells) and α-T (0.91 nmol/10 6 cells) were observed. Hepatocytes exposed to unesterified α-tocopherol (α-T, 25 μM) or α-tocopheryl acetate (α-TA, 25 μM), however, were not protected from the toxic effect of chemicals even though these treatments resulted in the marked accumulation of cellular α-T (2.65 nmol/10 6 cells) and α-TA (2.3 nmol/10 6 cells), respectively. Our findings suggest that the supplementation of endogenous stores of α-T or α-TA does not promote protection against chemical toxicity and that α-TS cytoprotection results not from the accumulation of α-T but rather from the cellular presence of the intact α-TS molecule. Thus α-TS appears to possess cytoprotective properties that differ from other vitamin E congeners.