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

Reference32 articles.

1. Acute Liver Failure

2. Paracetamol Overdosage Pharmacological Considerations and Clinical Management

3. Mechanism of paracetamol toxicity

4. Loss of CYP2E1 and CYP1A2 Activity as a Function of Acetaminophen Dose: Relation to Toxicity

5. Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics

Cited by 281 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Deciphering Acetaminophen-Induced Hepatotoxicity: The Crucial Role of Transcription Factors like Nuclear Factor Erythroid 2–Related Factor 2 as Genetic Determinants of Susceptibility to Drug-Induced Liver Injury;Drug Metabolism and Disposition;2024-06-10

2. Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) <i>via</i> dephosphorylation of the EGFR signaling pathway;The Journal of Biomedical Research;2024

3. Determination of Regulation of Drug Metabolizing Enzymes and Transporters;Oral Bioavailability and Drug Delivery;2023-10-10

4. Constitutive androstane receptor-responsive elements for mouse Cyp1a2 transcriptional activation induced by constitutive androstane receptor ligands;Drug Metabolism and Pharmacokinetics;2023-02

5. Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations;Phytomedicine;2023-01