Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR
- PMID: 12376703
- DOI: 10.1126/science.1073502
Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR
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.
Comment in
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Toxicology. Protecting liver from painkiller's lethal dose.Science. 2002 Oct 11;298(5592):341-2. doi: 10.1126/science.298.5592.341a. Science. 2002. PMID: 12376675 No abstract available.
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