Murase T, Masuda R, Aoi K, Sawamura T, Shiozaki Y, Sameshima Y
Jpn J Pharmacol. 1985 Feb;37(2):151-8. doi: 10.1254/jjp.37.151.
The effect of galactosamine on hepatic drug metabolizing activities was examined in rats. In the microsomal fraction, the contents of cytochrome P-450 (P-450) and cytochrome b5 (b5) and the activity of NADPH-cytochrome c reductase (reductase) were examined for 7 days after galactosamine administration. In addition, substrate metabolizing activities in damaged microsomes were examined using four substrates: aminopyrine, aniline, benzo(a)pyrene (B(a)P) and 7-ethoxycoumarine (7-EC). The contents of P-450 and b5 and the activity of reductase showed a minimal value after 3 days of galactosamine administration and then gradually increased, reaching to the control level after 7 days. All four substrate metabolizing activities showed a similar response as the content of P-450, but the decrement among the four activities was not uniform. The activities of B(a)P hydroxylation and 7-EC deethylation were more impared than those of aminopyrine demethylation and aniline hydroxylation. This nonuniformity was clear on the activity based on P-450. This result suggested that galactosamine disturbed the population of multiple P-450 subtypes, and each P-450 subtype was damaged to the various extent by galactosamine administration.
在大鼠中研究了半乳糖胺对肝脏药物代谢活性的影响。在微粒体部分，于给予半乳糖胺后7天检测细胞色素P - 450（P - 450）和细胞色素b5（b5）的含量以及NADPH - 细胞色素c还原酶（还原酶）的活性。此外，使用四种底物：氨基比林、苯胺、苯并(a)芘（B(a)P）和7 - 乙氧基香豆素（7 - EC）检测受损微粒体中的底物代谢活性。给予半乳糖胺3天后，P - 450和b5的含量以及还原酶的活性显示出最小值，然后逐渐增加，7天后达到对照水平。所有四种底物代谢活性均表现出与P - 450含量相似的反应，但四种活性之间的下降并不一致。苯并(a)芘羟化和7 - EC脱乙基的活性比氨基比林去甲基化和苯胺羟化的活性受损更严重。基于P - 450的活性，这种不一致性很明显。该结果表明，半乳糖胺扰乱了多种P - 450亚型的数量，并且给予半乳糖胺后每种P - 450亚型受到不同程度的损伤。
