Modulation of Acetaminophen-Induced Hepatotoxicity by the Xenobiotic Receptor CAR-Reference-Cited by-同舟云学术

Modulation of Acetaminophen-Induced Hepatotoxicity by the Xenobiotic Receptor CAR

Published:2002-10-11 Issue:5592 Volume:298 Page:422-424
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zhang Jun¹,Huang Wendong¹,Chua Steven S.¹,Wei Ping¹,Moore David D.¹

Affiliation:

1. Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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