Disturbance of Hepatic and Intestinal UDP-glucuronosyltransferase in Rats with Trinitrobenzene Sulfonic Acid–induced Colitis

Xueyan ZHOU; Yang XIE; Qu QI; Xuefang CHENG; Fang LIU; Ke LIAO; Guangji WANG; Haiping HAO

doi:10.2133/dmpk.DMPK-12-RG-097

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Disturbance of Hepatic and Intestinal UDP-glucuronosyltransferase in Rats with Trinitrobenzene Sulfonic Acid–induced Colitis

Xueyan ZHOU, Yang XIE, Qu QI, Xuefang CHENG, Fang LIU, Ke LIAO, Guangji WANG, Haiping HAO

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Xueyan ZHOU
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Yang XIE
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Qu QI
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Xuefang CHENG
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Fang LIU
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Ke LIAO
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Guangji WANG
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
Haiping HAO
State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University

Keywords: AhR, PPAR, PXR, FXR, nuclear receptors, phase II drug metabolism, UDP-glucuronosyltransferases, cytokines, inflammation, membrane barriers

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Supplementary material

2013 Volume 28 Issue 4 Pages 305-313

DOI https://doi.org/10.2133/dmpk.DMPK-12-RG-097

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Abstract

UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying various substances and in the pathological procedures of some diseases. The present study aims to uncover the potential dysregulation pattern of UGTs in trinitrobenzene sulfonic acid (TNBS)–induced colitis. Colitis was induced by intra-rectally administering a single dose of TNBS (100 mg/kg). The expression and enzyme activity of hepatic UGTs of colitis rats were all down-regulated significantly except UGT1A7, for which the mRNA level was up-regulated. In contrast, UGT isoforms in the small intestine were relatively unaffected. In the colon, where the inflammation occurs, the mRNA level and enzyme activity of UGT1A1 and 1A6 were down-regulated, but those of UGT1A7 and 2B1 up-regulated. The mRNA levels of various transcription factors, including AhR, CAR, PXR, PPARγ, and FXR were all decreased, except for AhR and CAR in the small intestine and colon. Our data suggests that colitis induces an isoform-dependent and tissue-specific dysregulation of UGTs and their related transcription factors.

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