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Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium
Huang Y.2; Hu N.2; Gao X.2; Yan Z.2; Li S.2; Jing W.2; Yan R.2
2015-05-05
Source PublicationChemico-Biological Interactions
ISSN18727786 00092797
Volume232Pages:38-48
Abstract

Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7 days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression.

KeywordCytochrome P450s Dextran Sulfate Sodium - Experimental Colitis Metabolism Testosterone
DOI10.1016/j.cbi.2015.02.013
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:000353741300006
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.First People's Hospital of Changzhou
2.Universidade de Macau
Recommended Citation
GB/T 7714
Huang Y.,Hu N.,Gao X.,et al. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium[J]. Chemico-Biological Interactions,2015,232:38-48.
APA Huang Y..,Hu N..,Gao X..,Yan Z..,Li S..,...&Yan R..(2015).Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.Chemico-Biological Interactions,232,38-48.
MLA Huang Y.,et al."Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium".Chemico-Biological Interactions 232(2015):38-48.
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