Johansson I, Ingelman-Sundberg M
FEBS Lett. 1985 Apr 22;183(2):265-9. doi: 10.1016/0014-5793(85)80790-0.
Treatment of rats with ethanol or rabbits with either imidazole or pyrazole, agents known to induce the ethanol-inducible form of liver microsomal cytochrome P-450 (P-450 LMeb), caused, compared to controls, 3-25-fold enhanced rates of CCl4-dependent lipid peroxidation or chloroform production in isolated liver microsomes. No significant differences were seen when the rate of CCl4-dependent lipid peroxidation was expressed relative to the amount of P-450 LMeb in the various types of microsomal preparations. In reconstituted membranous systems, this type of P-450 was a 100-fold more effective catalyst of CCl4 metabolism than either of the cytochromes P-450 LM2 or P-450 LM4. It is proposed that the induction of this isozyme provides the explanation on a molecular level for the synergism seen of ethanol on CCl4-dependent hepatotoxicity.
用乙醇处理大鼠，或用咪唑或吡唑处理兔子，已知这些试剂可诱导肝微粒体细胞色素P-450（P-450 LMeb）的乙醇诱导形式，与对照组相比，在分离的肝微粒体中，四氯化碳依赖性脂质过氧化率或氯仿生成率提高了3至25倍。当以各种类型微粒体制剂中P-450 LMeb的量为相对标准来表示四氯化碳依赖性脂质过氧化率时，未观察到显著差异。在重组膜系统中，这种类型的P-450对四氯化碳代谢的催化效率比细胞色素P-450 LM2或P-450 LM4中的任何一种都高100倍。有人提出，这种同工酶的诱导在分子水平上解释了乙醇对四氯化碳依赖性肝毒性的协同作用。
