Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR

被引：255

作者：

Zhang, J ^{[1
]}

Huang, WD ^{[1
]}

Chua, SS ^{[1
]}

Wei, P ^{[1
]}

Moore, DD ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

SCIENCE | 2002年 / 298卷 / 5592期

关键词：

D O I：

10.1126/science.1073502

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR null mice, and the CAR null mice were resistant to acetaminophen toxicity. Inhibition of CAR activity by administration of the inverse agonist ligand androstanol 1 hour after acetaminophen treatment blocked hepatotoxicity in wild type but not in CAR null mice. These results suggest an innovative therapeutic approach for treating the adverse effects of acetaminophen and potentially other hepatotoxic agents.

引用

页码：422 / 424

页数：3

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