Casini A F, Pompella A, Comporti M
Am J Pathol. 1985 Feb;118(2):225-37.
The mechanisms of bromobenzene and iodobenzene hepatotoxicity in vivo were studied in mice. Both the intoxications caused a progressive decrease in hepatic glutathione content. In both instances liver necrosis was evident only when the hepatic glutathione depletion reached a threshold value (3.5-2.5 nmol/mg protein). The same threshold value was evident for the occurrence of lipid peroxidation. Similar results were obtained in a group of mice sacrificed 15-20 hours after the administration of diethylmaleate, a drug which is mainly conjugated with hepatic glutathione without previous metabolism. The correlation between lipid peroxidation and liver necrosis was much more significant than that between covalent binding and liver necrosis. This fact supports the view that lipid peroxidation is the major candidate for the liver cell death produced by bromobenzene intoxication. Moreover, a dissociation of liver necrosis from covalent binding was observed in experiments in which Trolox C (a lower homolog of vitamin E) was administered after bromobenzene poisoning. The treatment with Trolox C, in fact, almost completely prevented both liver necrosis and lipid peroxidation, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein.
在小鼠体内研究了溴苯和碘苯肝毒性的机制。两种中毒情况均导致肝脏谷胱甘肽含量逐渐下降。在这两种情况下，只有当肝脏谷胱甘肽耗竭达到阈值（3.5 - 2.5 nmol/mg蛋白质）时，肝坏死才明显。脂质过氧化的发生也有相同的阈值。在给予马来酸二乙酯（一种主要与肝脏谷胱甘肽结合而无前期代谢的药物）后15 - 20小时处死的一组小鼠中获得了类似结果。脂质过氧化与肝坏死之间的相关性比共价结合与肝坏死之间的相关性更显著。这一事实支持了脂质过氧化是溴苯中毒导致肝细胞死亡的主要候选因素这一观点。此外，在溴苯中毒后给予生育酚类似物Trolox C（维生素E的一种低级同系物）的实验中，观察到肝坏死与共价结合的分离。事实上，用Trolox C治疗几乎完全预防了肝坏死和脂质过氧化，而溴苯代谢产物与肝脏蛋白质的共价结合程度则完全没有改变。
