Krikun G, Cederbaum A I
Biochem Pharmacol. 1985 Aug 15;34(16):2929-35. doi: 10.1016/0006-2952(85)90018-8.
Rat liver microsomes catalyze the oxidation of hydroxyl radical scavenging agents by an iron-dependent process, and can oxidize alcohols by pathways dependent on, as well as independent of, .OH. Experiments were carried out to evaluate which microsomal components participate in the production of .OH, and in the two pathways of oxidation of alcohols. Cobalt protoporphyrin IX treatment of rats resulted in a decrease in microsomal oxidation of aminopyrine, .OH scavengers, and alcohols. However, this treatment not only lowered the content of cytochrome P-450, but also decreased the activity of NADPH-cytochrome P-450 reductase. Carbon monoxide, metyrapone and SKF-525A also inhibited the oxidation of aminopyrine but did not affect oxidation of .OH scavengers. Desferrioxamine, a potent iron chelator, inhibited the oxidation of .OH scavengers but not aminopyrine. The oxidation of alcohols was partly sensitive to desferrioxamine and partly sensitive to carbon monoxide, thus showing similarities to the oxidation of .OH scavengers and drugs. These results suggest that the desferrioxamine-sensitive, .OH-dependent pathway of alcohol oxidation is mediated by the reductase, in analogy to results with .OH scavengers, whereas the desferrioxamine-resistant pathway of alcohol oxidation is mediated by cytochrome P-450, in analogy to results with aminopyrine. By the use of desferrioxamine or carbon monoxide, either of the two alcohol-oxidizing pathways can be inhibited independently of each other.
大鼠肝微粒体通过铁依赖过程催化羟基自由基清除剂的氧化，并且可以通过依赖于以及独立于·OH的途径氧化醇类。进行实验以评估哪些微粒体成分参与·OH的产生以及醇类氧化的两条途径。用钴原卟啉IX处理大鼠导致微粒体对氨基比林、·OH清除剂和醇类的氧化作用降低。然而，这种处理不仅降低了细胞色素P - 450的含量，还降低了NADPH - 细胞色素P - 450还原酶的活性。一氧化碳、甲吡酮和SKF - 525A也抑制了对氨基比林的氧化，但不影响·OH清除剂的氧化。强力铁螯合剂去铁胺抑制·OH清除剂的氧化，但不抑制对氨基比林的氧化。醇类的氧化部分对去铁胺敏感，部分对一氧化碳敏感，因此与·OH清除剂和药物的氧化表现出相似性。这些结果表明，类似于·OH清除剂的结果，醇类氧化的去铁胺敏感的、依赖于·OH的途径由还原酶介导，而醇类氧化的去铁胺抗性途径由细胞色素P - 450介导，类似于对氨基比林的结果。通过使用去铁胺或一氧化碳，可以相互独立地抑制两条醇类氧化途径中的任何一条。
