汞和镉中毒对肝脏微粒体CYP2E和CYP3A亚家族的影响。

Influence of mercury and cadmium intoxication on hepatic microsomal CYP2E and CYP3A subfamilies.

作者信息

Alexidis A N, Rekka E A, Kourounakis P N

机构信息

Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.

出版信息

Res Commun Mol Pathol Pharmacol. 1994 Jul;85(1):67-72.

PMID:7953196

Abstract

The effects of subchronic mercuric acetate and of acute mercuric acetate and cadmium chloride administration to rat hepatic microsomal protein and total cytochrome P450, as well as on p-nitrophenol hydroxylase (CYP2E) and erythromycin N-demethylase (CYP3A) activities were examined. It was found that Hg2+ and Cd2+ intoxication resulted in a significant decrease of total cytochrome P450 content. Acute Hg2+ and Cd2+ exposure decreased microsomal protein level. These metals also reduced CYP2E1 activity, while they did not seem to alter CYP3A1-mediated drug metabolism. This effect on CYP2E1 may be connected to free radical generation during Hg2+ and Cd2+ intoxication. Investigation is in progress using more P450 markers for elucidation of the effect of Hg2+ and Cd2+ on P450 activities.

摘要

研究了对大鼠肝微粒体蛋白、总细胞色素P450以及对硝基苯酚羟化酶（CYP2E）和红霉素N-脱甲基酶（CYP3A）活性进行亚慢性醋酸汞给药以及急性醋酸汞和氯化镉给药的影响。结果发现，汞离子（Hg2+）和镉离子（Cd2+）中毒导致总细胞色素P450含量显著降低。急性Hg2+和Cd2+暴露降低了微粒体蛋白水平。这些金属还降低了CYP2E1活性，而它们似乎并未改变CYP3A1介导的药物代谢。对CYP2E1的这种影响可能与Hg2+和Cd2+中毒期间自由基的产生有关。目前正在进行研究，使用更多的P450标志物来阐明Hg2+和Cd2+对P450活性的影响。