抄録
Treatment of cultured rat hepatocytes with 10μM 1-chloro-2, 4-dinitrobenzene (CDNB) resulted in an acute loss of cellular glu-tathione (GSH) within 30 min and a marked increase in spontaneous lactic dehydrogenase (LDH) leakage to the culture medium after 24 h, with obvious cellular degeneration as viewed by phase-contrast microscopy. Simultaneous treatment of the cells with α-tocopherol markedly protected the cells not only against LDH leakage but cellular degeneration in a dose-dependent manner. The EC50 of α-tocopherol was 0.1μM, ca. 200 times less than normal plasma levels in the rat. In response to the inhibitory effects of α-tocopherol on the cytolysis as measured by LDH leakage, GSH biosynthesis was stimulated by CDNB, and cellular GSH levels returned to control levels. The recovery was inhibited by 0.2mM buthionine-SR-sulfoximine (BSO), a specific inhibitor of γ-glutamylcys-teine synthetase. However, the stimulation of GSH biosynthesis ap-parently was not essential for the protection from cytolysis by GSH depletion during the experimental period, because treatment with 0.2mM BSO and 20μM tocopherol completely protected the cells against the lysis induced by BSO up to 32h without cellular GSH recovery. The results suggest that α-tocopherol may be a primary natural inhibitor of the cytolysis induced by xenobiotics which consume the cellular GSH in vivo.
