De Groot H, Sies H
Institut für Physiologische Chemie I, Universität Düsseldorf, West Germany.
Drug Metab Rev. 1989;20(2-4):275-84. doi: 10.3109/03602538909103543.
A variety of organic compounds such as carbon tetrachloride, halothane, gentian violet, and benznidazole are reductively metabolized to free radicals by liver microsomal cytochrome P-450. Due to the fact that this metabolic activation occurs at a site where O2 usually becomes activated during the monooxygenase cycle, there is a competition between these xenobiotics and O2 for electrons. Reductive activation occurs at a maximal rate under anaerobic conditions. Cell injury may be directly produced by the reactive metabolites. It may also result from lipid peroxidation induced by interaction of the free radicals with polyunsaturated fatty acids of membrane phospholipids. For polyhalogenated alkanes the latter process is most likely the one leading to cell death. When loss of cell viability is mediated by lipid peroxidation, a complex O2 dependence may result, characterized by a maximum loss of cell viability at oxygen partial pressures (PO2) between 1 and 10 mm Hg. These PO2 values are found in the centrilobular area of the liver lobule.
多种有机化合物，如四氯化碳、氟烷、龙胆紫和苯硝唑，可被肝微粒体细胞色素P - 450还原代谢为自由基。由于这种代谢活化发生在单加氧酶循环中O2通常被活化的位点，这些外源化合物与O2之间存在电子竞争。还原活化在厌氧条件下以最大速率发生。活性代谢产物可能直接导致细胞损伤。它也可能由自由基与膜磷脂的多不饱和脂肪酸相互作用诱导的脂质过氧化引起。对于多卤代烷烃，后一过程很可能是导致细胞死亡的原因。当细胞活力丧失由脂质过氧化介导时，可能会导致复杂的O2依赖性，其特征是在氧分压（PO2）为1至10 mmHg之间时细胞活力丧失最大。这些PO2值出现在肝小叶的小叶中心区域。
