Fernandez-Checa J C, Ookhtens M, Kaplowitz N
J Clin Invest. 1987 Jul;80(1):57-62. doi: 10.1172/JCI113063.
Hepatocytes from rats that were fed ethanol chronically for 6-8 wk were found to have a modest decrease in cytosolic GSH (24%) and a marked decrease in mitochondrial GSH (65%) as compared with pair-fed controls. Incubation of hepatocytes from ethanol-fed rats for 4 h in modified Fisher's medium revealed a greater absolute and fractional GSH efflux rate than controls with maintenance of constant cellular GSH, indicating increased net GSH synthesis. Inhibition of gamma-glutamyltransferase had no effect on these results, which indicates that no degradation of GSH had occurred during these studies. Enhanced fractional efflux was also noted in the perfused livers from ethanol-fed rats. Incubation of hepatocytes in medium containing up to 50 mM ethanol had no effect on cellular GSH, accumulation of GSH in the medium, or cell viability. Thus, chronic ethanol feeding causes a modest fall in cytosolic and a marked fall in mitochondrial GSH. Fractional GSH efflux and therefore synthesis are increased under basal conditions by chronic ethanol feeding, whereas the cellular concentration of GSH drops to a lower steady state level. Incubation of hepatocytes with ethanol indicates that it has no direct, acute effect on hepatic GSH homeostasis.
与配对喂养的对照组相比，发现长期喂食乙醇6 - 8周的大鼠肝细胞的胞质谷胱甘肽（GSH）适度降低（24%），线粒体GSH显著降低（65%）。在改良的Fisher培养基中，将喂食乙醇的大鼠的肝细胞孵育4小时，结果显示，与对照组相比，GSH的绝对流出率和分数流出率更高，同时细胞内GSH保持恒定，这表明GSH的净合成增加。抑制γ-谷氨酰转移酶对这些结果没有影响，这表明在这些研究过程中没有发生GSH的降解。在喂食乙醇的大鼠的灌注肝脏中也观察到分数流出增强。将肝细胞在含有高达50 mM乙醇的培养基中孵育，对细胞内GSH、培养基中GSH的积累或细胞活力没有影响。因此，长期喂食乙醇会导致胞质GSH适度下降，线粒体GSH显著下降。长期喂食乙醇会使基础条件下的GSH分数流出增加，进而导致合成增加，而细胞内GSH浓度则降至较低的稳态水平。用乙醇孵育肝细胞表明，乙醇对肝脏GSH稳态没有直接的急性影响。
