Nordmann R, Rouach H
Bull Acad Natl Med. 1995 Dec;179(9):1839-50; discussion 1850-3.
An oxidative stress occurs in the liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active " fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake.
在给予大鼠不同条件的乙醇后，其肝脏会发生氧化应激。乙醇诱导的细胞色素P450 2E1在氧化应激的产生中起关键作用，细胞内非血红素铁“氧化还原活性”部分的增加有利于该酶的生成。给予乙醇会引发1-羟乙基自由基的产生，该自由基已在体内得到确认。其反应性导致酒精诱导的免疫紊乱。长期给予乙醇并搭配高脂肪饮食可在大鼠身上重现肝脏炎症和纤维化疾病。这些疾病的严重程度与氧化应激的强度相关。给大鼠的某些乙醇给药条件也会在心肌和中枢神经系统引发氧化应激。通过其对谷氨酰胺合成酶活性的抑制作用及由此产生的兴奋性毒性，它可能导致神经元死亡，并可能导致对酒精的依赖。在酒精性个体的血清、红细胞以及肝活检中也报告了与氧化应激相关的疾病。对它们的检测可能有助于追踪酒精性肝病的进展。对于大量饮用酒精饮料的个体，可考虑补充抗氧化剂如维生素E以预防严重的细胞紊乱。自由基产生的增加可能在因大量且间歇性摄入乙醇导致的反复戒断所引发的严重细胞损伤的诱导中起作用。
