title: Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.
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 7days 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Department of Clinical Pharmacy, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Wanghui
authors.initials: W
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. Electronic address: ruyan@umac.mo.
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
chemical_list: D016207:Cytokines; D013739:Testosterone; D009195:Peroxidase; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C456179:Cyp2a1 protein, rat; C465260:Cyp3a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase
keywords: Cytochrome P450s; Dextran sulfate sodium; Experimental colitis; Metabolism; Testosterone