title: Disturbance of hepatic and intestinal UDP-glucuronosyltransferase in rats with trinitrobenzene sulfonic acid-induced colitis.
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.
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.forename: Qu
authors.initials: Q
authors.lastname: Qi
authors.forename: Xuefang
authors.initials: X
authors.lastname: Cheng
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ke
authors.initials: K
authors.lastname: Liao
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D000090702:Constitutive Androstane Receptor; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D000099148:UGT1A1 Enzyme
chemical_list: D000090702:Constitutive Androstane Receptor; D014453:Glucuronosyltransferase; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014302:Trinitrobenzenesulfonic Acid; D000099148:UGT1A1 Enzyme