Gumbrecht J R, Franklin M R
Drug Metab Dispos. 1983 Jul-Aug;11(4):312-8.
Two centrilobular hepatotoxins, bromobenzene and acetaminophen, and a periportal hepatotoxin, allyl alcohol, caused necrosis and cytochrome P-450 depletion in the livers of uninduced and phenobarbital-induced rats. The per cent loss of cytochrome P-450 and its enzymatic activity exceeded the amount of hepatic necrosis evident by light microscopy, indicating limitations to the use of regioselective hepatotoxins as probes for the intralobular localization of cytochrome P-450 functions. No hepatotoxin was specific for a single cytochrome P-450 subpopulation as defined either by DEAE-cellulose fractionation or by the ability to form metabolic intermediate complexes from two classes of substrates, but some selectivity was apparent. The susceptibilities of subpopulations as defined by DEAE fractionation to hepatotoxin-linked depletion differed in phenobarbital-induced and uninduced rats.
两种小叶中央区肝毒素，溴苯和对乙酰氨基酚，以及一种门周区肝毒素，烯丙醇，在未诱导和苯巴比妥诱导的大鼠肝脏中均引起坏死和细胞色素P-450耗竭。细胞色素P-450及其酶活性的损失百分比超过了光镜下明显可见的肝坏死量，这表明使用区域选择性肝毒素作为细胞色素P-450功能小叶内定位探针存在局限性。没有一种肝毒素对通过DEAE-纤维素分级分离或从两类底物形成代谢中间复合物的能力所定义的单个细胞色素P-450亚群具有特异性，但存在一些选择性。通过DEAE分级分离所定义的亚群对肝毒素相关耗竭的敏感性在苯巴比妥诱导和未诱导的大鼠中有所不同。
