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Characterization of hepatic drug-metabolizing activities of Bama miniature pigs (Sus scrofa domestica): Comparison with human enzyme analogs
Li, Jian; Liu, Yong; Zhang, Jiang-Wei; Wei, Hong; Yang, Ling
Source PublicationCOMPARATIVE MEDICINE
2006-08-01
Volume56Issue:4Pages:286-290
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectVeterinary Sciences ; Zoology
WOS Research AreaVeterinary Sciences ; Zoology
WOS KeywordLIVER-MICROSOMES ; CYTOCHROME-P450 2E1 ; IN-VITRO ; IDENTIFICATION ; DEXTROMETHORPHAN ; HEPATOCYTES ; INHIBITORS ; ISOENZYMES
AbstractWe used various substrates and selective inhibitors of human cytochrome P450 (CYP) isozymes as probes to study the metabolism of liver microsomes from Chinese Bama miniature pigs. Nifedipine oxidation (NOD) and testosterone 6 beta-hydroxylation (6 beta-OHT) activities were similar between human liver microsomes and those from Bama miniature pigs. However, compared with those from humans, liver microsomes from Bama miniature pigs showed decreased phenacetin O-deethylation, coumarin 7-hydroxylation, and chlorzoxazone 6-hydroxylation activities, whereas dextromethorphan O-demethylation activity was increased. Ketoconazole selectively inhibited NOD and 6 beta-OHT activities in microsomes from Bama pigs, and 8-methoxypsoralen and tranylcypromine inhibited coumarin 7-hydroxylation in pig microsomes. However, furafylline and quinidine failed to selectively inhibit phenacetin O-deethylation and dextromethorphan O-demethylation in microsomes from Bama pigs, whereas chlormethiazole more efficiently inhibited coumarin 7-hydroxylation activity than chlorzoxazone 6-hydroxylation in pig microsomes. Our results suggest that liver microsomes from Chinese Bama miniature pigs are similar to those from humans in regard to metabolism of nifedipine and testosterone (both are probe substrates for human CYP3A4). In addition, chemical inhibitors used as specific probes for human P450 enzymes did not always show the same selectivity toward corresponding enzyme activities in liver microsomes from Bama pigs. However, ketoconazole (a potent inhibitor of human CYP3A4) could be used as a selective inhibitor probe for the NOD and 6 beta-OHT activities in liver microsomes from Chinese Bama miniature pigs.
Language英语
WOS IDWOS:000240278800008
Citation statistics
Cited Times:34[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/140242
Collection中国科学院大连化学物理研究所
Affiliation1.Third Mil Med Univ, Dept Anim Sci, Coll Basic Med, Chongqing, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Li, Jian,Liu, Yong,Zhang, Jiang-Wei,et al. Characterization of hepatic drug-metabolizing activities of Bama miniature pigs (Sus scrofa domestica): Comparison with human enzyme analogs[J]. COMPARATIVE MEDICINE,2006,56(4):286-290.
APA Li, Jian,Liu, Yong,Zhang, Jiang-Wei,Wei, Hong,&Yang, Ling.(2006).Characterization of hepatic drug-metabolizing activities of Bama miniature pigs (Sus scrofa domestica): Comparison with human enzyme analogs.COMPARATIVE MEDICINE,56(4),286-290.
MLA Li, Jian,et al."Characterization of hepatic drug-metabolizing activities of Bama miniature pigs (Sus scrofa domestica): Comparison with human enzyme analogs".COMPARATIVE MEDICINE 56.4(2006):286-290.
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