Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Science (New York, N.Y.) | Oct 11, 2002

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.

Pubmed ID: 12376703 RIS Download

Mesh terms: Acetaminophen | Acetylcysteine | Alanine Transaminase | Analgesics, Non-Narcotic | Androstanols | Animals | Aryl Hydrocarbon Hydroxylases | Benzoquinones | Cytochrome P-450 CYP1A2 | Cytochrome P-450 CYP2E1 | Cytochrome P-450 CYP3A | Cytochrome P-450 Enzyme System | Glutathione | Glutathione S-Transferase pi | Glutathione Transferase | Humans | Imines | Isoenzymes | Liver | Mice | Mice, Knockout | Mice, Transgenic | Oxidoreductases, N-Demethylating | Phenobarbital | Pyridines | RNA, Messenger | Receptors, Cytoplasmic and Nuclear | Time Factors | Transcription Factors

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK46546

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.