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Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450 activities in rat liver, kidney and intestine
Hu, Nan1,3; Huang, Yanjuan1; Gao, Xuejiao1; Li, Sai1; Yan, Zhixiang1; Wei, Bin1; Yan, Ru1,2
2017-06
Source PublicationCHEMICO-BIOLOGICAL INTERACTIONS
ISSN0009-2797
Volume271Pages:48-58
Abstract

Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs) have been reported in this model and patients with UC. In this study, six CYPs activities were quantitatively determined in microsomes of liver (RLMs), kidney (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days, UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases and compared with normal rats. Generally, CYPs activities varied with isoform, organ, and disease status. Hepatic CYP1A2, 2B1, 2C6/11, 2E1 and 3A1/2 activities were reduced by acute colitis and completely or partially restored after DSS was halted. Although DSS treatment decreased the V-max of renal CYP2C6/11 and increased that of CYP2D2, their CLint, in vitro were comparable among normal, acute and remission stages. DSS treatment changed the kinetics of CYP3A1/2-mediated nifedipine metabolism in RRMs from biphasic to classical kinetics. Notably, CYP2D2 activity was elevated in liver and kidney in acute UC, while enhanced in liver and decreased in kidney in remission. In intestine, CYP3A1/2 activity was increased in UCA and further enhanced after DSS withdrawal. These findings highlight the necessity of quantifying enzyme activity for precision drug therapy. (C) 2017 Elsevier B.V. All rights reserved.

KeywordExperimental Colitis Dextran Sulfate Sodium Cyps Rat Liver Microsomes Rat Renal Microsomes Rat Intestinal Microsomes
DOIhttp://doi.org/10.1016/j.cbi.2017.04.018
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS SubjectBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS IDWOS:000402444300007
PublisherELSEVIER IRELAND LTD
The Source to ArticleWOS
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYan, Ru
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.UM Zhuhai Research Institute, No.1 Software Road, Zhuhai Hi-tech Zone, Guangdong, China
3.Department of Pharmacy, The First People's Hospital of Changzhou, Changzhou, Jiang Su, China.
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Hu, Nan,Huang, Yanjuan,Gao, Xuejiao,et al. Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450 activities in rat liver, kidney and intestine[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2017,271:48-58.
APA Hu, Nan.,Huang, Yanjuan.,Gao, Xuejiao.,Li, Sai.,Yan, Zhixiang.,...&Yan, Ru.(2017).Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450 activities in rat liver, kidney and intestine.CHEMICO-BIOLOGICAL INTERACTIONS,271,48-58.
MLA Hu, Nan,et al."Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450 activities in rat liver, kidney and intestine".CHEMICO-BIOLOGICAL INTERACTIONS 271(2017):48-58.
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