Induction of genes for metabolism and transport by trans-stilbene oxide in livers of Sprague-Dawley and Wistar-Kyoto rats.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Angela L SlittC D Klaassen

Abstract

trans-Stilbene oxide (TSO) is a synthetic proestrogen that induces phase I and II drug-metabolizing enzymes in rat liver. The purpose of this study was to determine whether TSO also induces transporter expression in rat liver and whether gene induction in rat liver after TSO occurs in a constitutive androstane receptor (CAR)-dependent manner. Total RNA was isolated from male rat livers after treatment with TSO for up to 4 days (200 mg/kg, i.p., twice daily), and the mRNA levels for each gene were quantified. CYP2B1/2, CYP3A1, epoxide hydrolase, heme oxygenase-1, UGT1A6, UGT2B1, multiple drug resistance protein (Mdr) 1a and 1b, as well as multidrug resistance-associated protein (Mrp) 2, 3, and 4 mRNA were increased in livers after TSO treatment. To determine whether TSO activates gene expression in a CAR-dependent manner, male and female Wistar-Kyoto (WKY) rats were treated with TSO for 3 days. TSO induced CYP2B1/2, UGT2B1, and Mdr1b in males more than in females, suggesting that TSO could increase their expression via CAR. Conversely, TSO induced CYP3A1, epoxide hydrolase, UGT1A6, and Mrp3 similarly in both genders, indicating that induction of these genes occurs independently of CAR. TSO treatment also increased the activity o...Continue Reading

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Feb 28, 2004·Molecular Endocrinology·Karen Swales, Masahiko Negishi

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Citations

Jul 30, 2009·Journal of Gastroenterology and Hepatology·Mario CongiuPaul V Desmond
Feb 2, 2010·Expert Opinion on Drug Metabolism & Toxicology·Haishan Li, Hongbing Wang
Mar 18, 2010·Drug Metabolism Reviews·Xinsheng Gu, Jose E Manautou
Dec 17, 2008·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Wolfgang HagmannJ Matthias Löhr
Sep 25, 2007·Chemistry & Biodiversity·Bernard Testa, Stefanie D Krämer
Aug 28, 2007·Journal of Biochemical and Molecular Toxicology·Andrew J LickteigNathan J Cherrington

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