Strubelt O, Younes M, Pentz R
Toxicology. 1987 Aug;45(2):213-23. doi: 10.1016/0300-483x(87)90107-7.
Ethanol at initial concentrations between 0.75 and 6 g/l produced a dose-dependent release of the enzymes glutamic-pyruvic-transaminase and sorbitol dehydrogenase (GPT, SDH) from the isolated perfused rat liver. At the concentration of 6 g/l, it also decreased the oxygen consumption and elevated the calcium content of the isolated livers. These toxic effects of ethanol were significantly enhanced in livers, the glutathione content of which had been depleted by pretreatment with phorone. Ethanol-induced toxicity in glutathione-depleted isolated livers could be prevented both by inhibition of alcohol dehydrogenase with 4-methylpyrazole and of xanthine oxidase with allopurinol. In rats, in vivo, 1.6 g/kg ethanol injected intravenously produced a small increase in serum GPT and SDH concentrations 4 h after its administration. This increase in enzyme activities was several-fold higher and longer lasting in rats pretreated with phorone. Glutathione depletion per se did not induce hepatotoxicity in vitro or in vivo. Since glutathione is involved in several lines of defense against oxidative damage, our results of an enhanced susceptibility of glutathione-depleted livers to ethanol toxicity favour the hypothesis that ethanol exerts its hepatotoxic action via an activation of molecular oxygen.
初始浓度在0.75至6克/升之间的乙醇会使离体灌注大鼠肝脏剂量依赖性地释放谷氨酸丙酮酸转氨酶和山梨醇脱氢酶（GPT、SDH）。在6克/升的浓度下，它还会降低离体肝脏的耗氧量并提高其钙含量。在用佛尔酮预处理使谷胱甘肽含量耗尽的肝脏中，乙醇的这些毒性作用会显著增强。乙醇诱导的谷胱甘肽耗尽的离体肝脏毒性，既可以通过用4 - 甲基吡唑抑制乙醇脱氢酶，也可以通过用别嘌呤醇抑制黄嘌呤氧化酶来预防。在大鼠体内，静脉注射1.6克/千克乙醇后4小时，血清GPT和SDH浓度会有小幅升高。在用佛尔酮预处理的大鼠中，这种酶活性的升高幅度更高且持续时间更长。谷胱甘肽耗竭本身在体外或体内均不会诱发肝毒性。由于谷胱甘肽参与了多条抗氧化损伤防御途径，我们关于谷胱甘肽耗尽的肝脏对乙醇毒性易感性增强的结果支持了乙醇通过激活分子氧发挥其肝毒性作用的假说。
