Nordmann R
Département de Recherches Biomédicales sur l'Alcoolisme, Université René-Descartes, Paris, France.
Alcohol Alcohol. 1994 Sep;29(5):513-22.
Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963) concerning the prevention of the acute ethanol-induced fatty liver by antioxidants, many observations have shown that ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation. Adaptative increases in some elements of the hepatic antioxidant defence partly counteract the enhanced generation of prooxidant free radicals following chronic ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is administered together with a fat-rich diet and/or various xenobiotics. Chronic ethanol feeding has also been reported to potentiate the oxidative stress resulting from an acute ethanol load. By generating potent chemoattractants for human neutrophils and/or by stimulating the expression of genes involved in collagen biosynthesis, liver lipid peroxidation may play an important role in the progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been shown not to be restricted to the liver, but also to affect, under some experimental conditions of ethanol administration, extrahepatic tissues, such as the central nervous system, the heart and the testes. This stress can be partly prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances have also been reported in clinical studies in blood and liver biopsies. Pharmacological antioxidants could have beneficial effects in reducing the incidence of ethanol-induced changes in cellular lipids, proteins and nucleic acids. The antioxidants considered could act by reducing free radical production (e.g. chelators of redox-active iron derivatives), trapping free radicals themselves, interrupting the peroxidation process or reinforcing the natural antioxidant defence.
继迪卢齐奥（《生理学家》6卷，第169 - 173页，1963年）关于抗氧化剂预防急性乙醇诱导的脂肪肝的开创性报告之后，许多观察结果表明，乙醇诱导的肝损伤可能至少部分与自由基产生增加和/或抗氧化防御能力下降所导致的氧化应激有关。本文综述了实验性急性和慢性乙醇给药后主要肝脏酶促和非酶促抗氧化系统所受到的干扰，强调了膳食α-生育酚在改变氧化应激诱导及其通常表现为脂质过氧化增加方面的重要作用。肝脏抗氧化防御的某些成分适应性增加，部分抵消了慢性乙醇摄入后促氧化自由基生成的增强。相比之下，当乙醇与富含脂肪的饮食和/或各种外源性物质一起给药时，脂质过氧化更易发生。据报道，慢性乙醇喂养还会增强急性乙醇负荷所导致的氧化应激。肝脏脂质过氧化通过产生对人类中性粒细胞有效的趋化因子和/或通过刺激参与胶原蛋白生物合成的基因表达，可能在脂肪变性发展为肝炎和肝硬化的过程中起重要作用。氧化应激已被证明不仅局限于肝脏，在某些乙醇给药的实验条件下，还会影响肝外组织，如中枢神经系统、心脏和睾丸。补充维生素E可部分预防这种应激。在血液和肝脏活检的临床研究中也报道了乙醇诱导的抗氧化干扰。药理抗氧化剂在降低乙醇诱导的细胞脂质、蛋白质和核酸变化发生率方面可能具有有益作用。所考虑的抗氧化剂可通过减少自由基产生（如氧化还原活性铁衍生物的螯合剂）、捕获自由基本身、中断过氧化过程或增强天然抗氧化防御来发挥作用。
