Induction of drug metabolism enzymes and transporters by oltipraz in rats.

Journal of Biochemical and Molecular Toxicology
Matthew D MerrellN J Cherrington

Abstract

Coordinate regulation of Phase-I and -II enzymes with xenobiotic transporters has been shown after treatment with microsomal enzyme inducers. The chemopreventive agent oltipraz (OPZ) induces Phase-I and -II drug-metabolizing enzymes such as CYP2B and NQO1. The purpose of this study was to examine the regulation of drug-metabolizing enzymes and transporters in response to OPZ treatment and to investigate a potential role for constitutive androstane receptor (CAR) in OPZ-mediated induction. Sprague-Dawley rats treated with OPZ exhibited increased mRNA and protein levels of both Nqo1 and Cyp2b1/2 by 24 h. To examine whether OPZ activates transporter gene expression via CAR, sexually dimorphic male and female Wistar-Kyoto (WKY) rats were treated with OPZ and mRNA levels quantified by bDNA signal amplification. OPZ induced Ugt1a6 and Ugt2b1 in males significantly higher than in females, indicating a CAR-dependent mechanism of induction. However, OPZ induced microsomal epoxide hydrolase, NAD(P)H quinone oxidoreductase, and Cyp3a1/23 equally in both genders, indicating a CAR-independent mechanism of induction of these genes. Similarly, the transporters Mdr1a, Mdr1b, Mrp3, and Mrp4 were induced by OPZ without any apparent difference be...Continue Reading

References

May 1, 1986·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S S AnsherE Bueding
Mar 30, 1983·Toxicology and Applied Pharmacology·J C Cook, E Hodgson
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·R Venugopal, A K Jaiswal
Nov 1, 1996·Carcinogenesis·T PrimianoT R Sutter
Jun 6, 1997·The Journal of Biological Chemistry·P Honkakoski, M Negishi
May 21, 1998·Pharmacology & Therapeutics·M L Clapper
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K MahéoA Guillouzo
Feb 23, 1999·Chemical Research in Toxicology·T W KenslerB D Roebuck
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Ramos-GomezT W Kensler
Jan 17, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·A L SlittC D Klaassen
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Susan C N BuistCurtis D Klaassen
Apr 19, 2002·The Journal of Pharmacology and Experimental Therapeutics·Ning LiCurtis D Klaassen
Jun 18, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James M BradyCurtis D Klaassen
Jan 16, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tyra M Leazer, Curtis D Klaassen
Aug 28, 2003·The Journal of Biological Chemistry·Il Je Cho, Sang Geon Kim
Oct 23, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nathan J CherringtonCurtis D Klaassen
Mar 23, 2005·Pharmacology & Therapeutics·Tony K L KiangThomas K H Chang
May 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Noam ZelcerPiet Borst
Jul 21, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew J LickteigNathan J Cherrington

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Citations

Apr 3, 2009·Archives of Toxicology·Martina DeckerAnnette Cronin
May 14, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew D MerrellNathan J Cherrington
Jan 28, 2010·Pharmacological Reviews·Curtis D Klaassen, Lauren M Aleksunes
Mar 18, 2010·Drug Metabolism Reviews·Xinsheng Gu, Jose E Manautou
Feb 19, 2015·Pharmacology Research & Perspectives·Sarina SchulzeKristina Endres
Aug 24, 2010·Advanced Drug Delivery Reviews·Antonia H Tolson, Hongbing Wang
Jul 1, 2009·Pharmacology & Therapeutics·Samuel Carroll BrooksSang Geon Kim

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