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[苯巴比妥和3-甲基胆蒽诱导及急性四氯化碳中毒后雄性大鼠肝微粒体细胞色素P450的选择性降低]

[A selective decrease in cytochrome P450 in the liver microsomes of male rats following phenobarbital and 3-methylcholanthrene induction and acute tetrachloromethane poisoning].

作者信息

Angelov E P

出版信息

Eksp Med Morfol. 1993;31(3-4):1-15.

PMID:7805614
Abstract

The liver microsomal content of cyt. P450 and b5 and activities of selected mixed-function oxidases were compared following phenobarbital (PB)- and 3-methylcholantrene (MC) induction and acute intoxication with carbontetrachloride (CT). PB increased the content of P450 and the activities of both NADPH-cytochrome c reductase and benzphetamin demethylase. MC increased only the content of cytochrome b5. CT after 4 hours damaged selectively the liver monoxidase components: 1. the activity of NADPH-cytochrome c reductase and the content of b5 were not changed in the three groups; 2. the content of P450 was decreased differently: more sensitive to the destructive effect of CT was the PB-inducible P450. Most resistant was the MC-inducible P450; 3. MC decreased the benzphetamin demethylation in control- and PB-microsomes in lower degree than the content of P450. The relative high rates of the benzphetamin demethylase after CT by PB-microsomes was explained by increased activity of NADPH-cytochrome c reductase in this group. The selective damaging effect of CT on P450 was interpreted by complex of local factors: metabolizing of CT to CCL3, lipid peroxidation, phospholipid microenvironment, pO2, antioxidants concentration, activity of heme degrading enzymes.

摘要

比较了苯巴比妥(PB)和3-甲基胆蒽(MC)诱导以及四氯化碳(CT)急性中毒后细胞色素P450和b5的肝微粒体含量以及所选混合功能氧化酶的活性。PB增加了P450的含量以及NADPH-细胞色素c还原酶和苄非他明脱甲基酶的活性。MC仅增加了细胞色素b5的含量。4小时后的CT选择性地损害了肝脏单氧化酶成分:1. 三组中NADPH-细胞色素c还原酶的活性和b5的含量未改变;2. P450的含量有不同程度的降低:对CT破坏作用更敏感的是PB诱导型P450。最具抗性的是MC诱导型P450;3. MC降低对照和PB微粒体中苄非他明脱甲基作用的程度低于P450的含量。PB微粒体在CT作用后苄非他明脱甲基酶相对较高的活性是由该组中NADPH-细胞色素c还原酶活性增加所解释的。CT对P450的选择性破坏作用是由局部因素的综合作用所解释的:CT代谢为三氯甲烷、脂质过氧化、磷脂微环境、pO2、抗氧化剂浓度、血红素降解酶的活性。

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