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Publication : Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR.

First Author  Zhang J Year  2002
Journal  Science Volume  298
Issue  5592 Pages  422-4
PubMed ID  12376703 Mgi Jnum  J:83102
Mgi Id  MGI:2656760 Doi  10.1126/science.1073502
Citation  Zhang J, et al. (2002) Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 298(5592):422-4
abstractText  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.
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