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低剂量二乙氨基二硫代甲酸盐可减轻大鼠体内1,3 - 二氯 - 2 - 丙醇的肝毒性,并选择性抑制细胞色素P450 2E1(CYP2E1)的活性。

Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat.

作者信息

Stott I, Murthy A, Robinson A, Thomas N W, Fry J R

机构信息

Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.

出版信息

Hum Exp Toxicol. 1997 May;16(5):262-6. doi: 10.1177/096032719701600505.

DOI:10.1177/096032719701600505
PMID:9192205
Abstract

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepatotoxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.

摘要

研究了低剂量二乙氨基二硫代甲酸盐(DEDC)对大鼠肝脏细胞色素P450依赖性酶活性及1,3 - 二氯 - 2 - 丙醇(DCP)肝毒性的影响。5mg/kg剂量的DEDC选择性抑制CYP2E1活性的酶标志物,并对DCP肝毒性提供显著保护。在较高剂量(25mg/kg)时,DEDC还抑制CYP1A2活性的酶标志物,并对DCP肝毒性提供完全保护。得出以下结论:(a)5mg/kg剂量的DEDC在大鼠体内是一种选择性CYP2E1抑制剂;(b)DCP肝毒性主要由CYP2E1介导,CYP1A2可能也有一定作用。

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