Maellaro E, Casini A F, Del Bello B, Comporti M
Istituto di Patologia Generale dell'Università di Siena, Italy.
Biochem Pharmacol. 1990 May 15;39(10):1513-21. doi: 10.1016/0006-2952(90)90515-m.
The mechanisms of the liver damage produced by three glutathione (GSH) depleting agents, bromobenzene, allyl alcohol and diethylmaleate, was investigated. The change in the antioxidant systems represented by alpha-tocopherol (vitamin E) and ascorbic acid were studied under conditions of severe GSH depletion. With each toxin liver necrosis was accompanied by lipid peroxidation that developed only after severe depletion of GSH. The hepatic level of vitamin E was decreased whenever extensive lipid peroxidation developed. In the case of bromobenzene intoxication, vitamin E decreased before the onset of lipid peroxidation. Changes in levels of the ascorbic and dehydroascorbic acid indicated a redox cycling of vitamin C with the oxidative stress induced by all the three agents. Such a change of the redox state of vitamin C (increase of the oxidized over the reduced form) may be an index of oxidative stress preceding lipid peroxidation in the case of bromobenzene. In the other cases, such a change is likely to be a consequence of lipid peroxidation. Experiments carried out with vitamin E deficient or supplemented diets indicated that the pathological phenomena occurring as a consequence of GSH depletion depend on hepatic levels of vitamin E. In vitamin E deficient animals, lipid peroxidation and liver necrosis appeared earlier than in animals fed the control diet. Animals fed a vitamin E supplemented diet had an hepatic vitamin E level double that obtained with a commercial pellet diet. In such animals, bromobenzene and allyl alcohol had only limited toxicity and diethylmaleate none in spite of comparable hepatic GSH depletion. Thus, vitamin E may largely modulate the expression of the toxicity by GSH depleting agents.
研究了三种耗竭谷胱甘肽（GSH）的试剂——溴苯、烯丙醇和马来酸二乙酯所导致的肝损伤机制。在严重GSH耗竭的条件下，研究了以α-生育酚（维生素E）和抗坏血酸为代表的抗氧化系统的变化。每种毒素导致的肝坏死均伴有脂质过氧化，且脂质过氧化仅在GSH严重耗竭后才发生。每当发生广泛的脂质过氧化时，肝脏中的维生素E水平就会降低。在溴苯中毒的情况下，维生素E在脂质过氧化开始之前就已降低。抗坏血酸和脱氢抗坏血酸水平的变化表明，维生素C在这三种试剂诱导的氧化应激下发生了氧化还原循环。在溴苯中毒的情况下，维生素C氧化还原状态的这种变化（氧化形式相对于还原形式增加）可能是脂质过氧化之前氧化应激的一个指标。在其他情况下，这种变化可能是脂质过氧化的结果。用缺乏或补充维生素E的饮食进行的实验表明，GSH耗竭导致的病理现象取决于肝脏中的维生素E水平。在缺乏维生素E的动物中，脂质过氧化和肝坏死比喂食对照饮食的动物出现得更早。喂食补充维生素E饮食的动物肝脏中的维生素E水平是商业颗粒饮食动物的两倍。在这些动物中，尽管肝脏中的GSH耗竭程度相当，但溴苯和烯丙醇的毒性有限，而马来酸二乙酯则无毒性。因此，维生素E可能在很大程度上调节了GSH耗竭试剂毒性的表达。
