| Literature DB >> 12376703 |
Jun Zhang1, Wendong Huang, Steven S Chua, Ping Wei, David D Moore.
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.Entities:
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Year: 2002 PMID： 12376703 DOI： 10.1126/science.1073502
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728