Okuno H, Hazama H, Murase T, Shiozaki Y, Sameshima Y
Jpn J Pharmacol. 1986 Jul;41(3):363-71. doi: 10.1254/jjp.41.363.
The drug metabolizing activity of rat liver during long-term administration of carbon tetrachloride (CCl4), and its relationship with the content of hydroxyproline (Hyp) in the liver were examined. The contents of cytochrome P-450 (P-450) and cytochrome b5 (b5) and the metabolization of aniline, aminopyrine, 7-ethoxycoumarin (7-EC) and benzo(a)pyrene (B(a)P) in the microsomal fraction were examined five days after the final administration of CCl4. The contents of P-450 and b5 and the activity to metabolize the four substrates were gradually reduced as the Hyp content in the liver increased. However, aminopyrine N-demethylation and B(a)P hydroxylation, particularly the latter, was more reduced than aniline hydroxylation and 7-EC O-deethylation in the early stage of hepatic fibrosis. Such differences may be due mainly to the different P-450 subtypes affected by CCl4.
研究了长期给予四氯化碳（CCl4）期间大鼠肝脏的药物代谢活性及其与肝脏中羟脯氨酸（Hyp）含量的关系。在最后一次给予CCl4五天后，检测微粒体部分中细胞色素P-450（P-450）和细胞色素b5（b5）的含量以及苯胺、氨基比林、7-乙氧基香豆素（7-EC）和苯并（a）芘（B（a）P）的代谢情况。随着肝脏中Hyp含量的增加，P-450和b5的含量以及代谢四种底物的活性逐渐降低。然而，在肝纤维化早期，氨基比林N-脱甲基化和B（a）P羟基化，尤其是后者，比苯胺羟基化和7-EC O-脱乙基化降低得更多。这种差异可能主要是由于受CCl4影响的不同P-450亚型所致。
