消草磷破坏肝脏细胞色素P450

消草磷与经苯巴比妥预处理大鼠的肝微粒体一起温育,在有NADPH存在时,最多可使肝微粒体细胞色素P450丢失58％左右。苯巴比妥预处理大鼠经ip或po 1.0g/kg消草磷,18h后肝微粒体P450将丢失40％左右,但用还原态P450甲吡酮络合物生成量估算剩余P450的亚族组成却无显著变化。此现象似提示消草磷的体内活性代谢物之一或许是硫化氢。尽管高剂量消草磷体内与体外均导致P450破坏,但低剂量(如 0.1g/kg)短期接触却不致诱发以肝脏P450丢失为特征的特殊肝脏毒性。

The hepatotoxicity characterized by the loss of P450 of amiprophos

After incubation of amiprophos (O-ethyl-O- (2-nitro-4 methylphenyl)-N-isopropyl thiono phosphoroamide) with liver microsomesof rats pretfeated with phenobarbital (PB) in the presence of NADPH, 58% of the microsomal cytochrome P450 would be lost at most. 18 h after ip or po l.0g/kg amiprophos, the microsomal P450 of PB pretreated rats decreased to 60% of control value, but the composition of subpopulations of P450 showed no significant change as estimated by the production of the complex compound of reduced form of P450 and mety rapone. These observations showed that one of the active metabolites of amiprophos in vivo might be H2S whichwas responsible for the loss of P450. Although high dose of amiprophos destroyed P450 in vivo as well as in vitro, lower dose (e. g. 0.lg/kg) and shorter term exposure would not induce rats to develop hepatotoxicity characterized by the loss of P450.