Fariss M W, Merson M H, O'Hara T M
Department of Pathology, Virginia Commonwealth University, Richmond 23298-0662.
Toxicol Lett. 1989 Apr;47(1):61-75. doi: 10.1016/0378-4274(89)90086-6.
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.
在有和没有细胞外钙（Ca2+）及琥珀酸生育酚酯（α-TS）的情况下，将大鼠和犬的肝细胞悬液暴露于有毒浓度的甲磺酸乙酯（EMS）和离子载体A-23187中。当暴露于“生理”细胞外游离钙浓度（0.8 - 1.5 mM）时，外源性给予α-TS（25 μM）可完全保护肝细胞免受化学诱导的毒性。在这些保护条件下，观察到α-TS（2.8 nmol/10(6) 个细胞）和α-生育酚（α-T，0.91 nmol/10(6) 个细胞）的细胞内积累。然而，暴露于未酯化的α-生育酚（α-T，25 μM）或α-生育酚乙酸酯（α-TA，25 μM）的肝细胞，即使这些处理分别导致细胞内α-T（2.65 nmol/10(6) 个细胞）和α-TA（2.3 nmol/10(6) 个细胞）的显著积累，也未免受化学物质的毒性作用。我们的研究结果表明，补充内源性α-T或α-TA储备并不能促进对化学毒性的保护，并且α-TS的细胞保护作用并非源于α-T的积累，而是源于完整α-TS分子在细胞内的存在。因此，α-TS似乎具有与其他维生素E同系物不同的细胞保护特性。
