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氯仿中毒时大鼠肝脏细胞色素P450分子种类的变化

Changes in cytochrome P450 molecular species in rat liver in chloroform intoxication.

作者信息

Enosawa S, Nakazawa Y

出版信息

Biochem Pharmacol. 1986 May 1;35(9):1555-60. doi: 10.1016/0006-2952(86)90124-3.

DOI:10.1016/0006-2952(86)90124-3
PMID:3707616
Abstract

The effect of CHCl3 on the composition of hepatic microsomal cytochrome P450 species was compared with that of CCl4 in rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (3MC). The administration of CHCl3 hardly affected cytochrome P450 content in non-treated rat liver, but caused a similar degree of depletion in the content as observed after CCl4 administration in PB-pretreated rats. In the pretreatment with 3MC, the administration of CHCl3 brought about a marked decrease in the content to 24% of control after 12 hr, while CCl4 reduced the content only to one-half of control. It was demonstrated by SDS-polyacrylamide gel electrophoresis and Whatman DE-52 anion-exchange chromatography that 3MC-induced P450 species decreased with CHCl3, while it was affected little by CCl4 treatment. The activity of benzo[a]pyrene hydroxylase was altered together with the change in the content of cytochrome P450 species. The administration of CHCl3 to PB-pretreated rats caused the depletion in PB-induced P450. These findings indicate that cytochrome P450 species induced with 3MC as well as PB are highly susceptible to CHCl3 intoxication, whereas the administration of CCl4 depletes the PB-induced species without affecting the 3MC-induced species.

摘要

在经苯巴比妥(PB)或3 - 甲基胆蒽(3MC)预处理的大鼠中,比较了氯仿(CHCl3)和四氯化碳(CCl4)对肝微粒体细胞色素P450种类组成的影响。氯仿的给药对未处理大鼠肝脏中的细胞色素P450含量几乎没有影响,但在PB预处理的大鼠中,其导致的含量减少程度与CCl4给药后观察到的相似。在用3MC预处理的情况下,氯仿给药12小时后使含量显著降低至对照的24%,而CCl4仅将含量降低至对照的一半。通过SDS - 聚丙烯酰胺凝胶电泳和Whatman DE - 52阴离子交换色谱法证明,3MC诱导的P450种类随氯仿减少,而CCl4处理对其影响很小。苯并[a]芘羟化酶的活性随细胞色素P450种类含量的变化而改变。对PB预处理的大鼠给予氯仿会导致PB诱导的P450减少。这些发现表明,3MC以及PB诱导的细胞色素P450种类对氯仿中毒高度敏感,而CCl4的给药会消耗PB诱导的种类,而不影响3MC诱导的种类。

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