Kretzschmar M, Reinhardt D, Schlechtweg J, Machnik G, Klinger W, Schirrmeister W
Clinic of Anaesthesiology and Intensive Care, Friedrich Schiller University Jena, Germany.
Exp Toxicol Pathol. 1992 Oct;44(6):344-8. doi: 10.1016/S0940-2993(11)80225-3.
The influence of chronic ethanol feeding to rats on the hepatic glutathione (GSH and GSSG) system (synthesis, catabolism, export) and on the GSH and GSSG concentrations in extrahepatic tissues was investigated. Histological examination of livers from ethanol pretreated rats revealed a minor dilatation of the hepatic sinusoids. After ethanol administration the distribution pattern of gamma-glutamyltranspeptidase (enzymehistochemistry) was nearly unchanged, but the hepatic activity of this enzyme was increased. The ethanol pretreatment led to a decrease in hepatic GSH content. The hepatic activity of the GSSG-reductase were increased after ethanol treatment whereas the activities of the GSH synthesizing enzymes (gamma-glutamyl-cysteinyl-synthetase and GSH-synthetase) were not affected. A strong increase in sinusoidal GSH export was found in the ethanol-pretreated rats. The GSH- and GSSG concentrations of brain, lung, kidney and skeletal muscle were unchanged. It can be concluded that the ethanol-induced alteration of the hepatic GSH metabolism is caused mainly by changes of the sinusoidal membrane of the hepatocytes (direct effect of ethanol on the sinusoidal GSH carrier) leading to an increased GSH export into plasma. This effect should not due to an increased extrahepatic requirement for GSH.
研究了长期给大鼠喂食乙醇对肝脏谷胱甘肽（GSH和GSSG）系统（合成、分解代谢、输出）以及对肝外组织中GSH和GSSG浓度的影响。对经乙醇预处理的大鼠肝脏进行组织学检查发现肝血窦有轻微扩张。给予乙醇后，γ-谷氨酰转肽酶的分布模式（酶组织化学）几乎未变，但该酶的肝脏活性增加。乙醇预处理导致肝脏GSH含量降低。乙醇处理后肝脏GSSG还原酶的活性增加，而GSH合成酶（γ-谷氨酰-半胱氨酸合成酶和GSH合成酶）的活性未受影响。在经乙醇预处理的大鼠中发现肝血窦GSH输出显著增加。脑、肺、肾和骨骼肌的GSH和GSSG浓度未变。可以得出结论，乙醇诱导的肝脏GSH代谢改变主要是由肝细胞肝血窦膜的变化（乙醇对肝血窦GSH载体的直接作用）导致GSH向血浆中的输出增加引起的。这种作用不应归因于肝外对GSH需求的增加。
