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题名: Characterization of hepatic drug-metabolizing activities of Bama miniature pigs (Sus scrofa domestica): Comparison with human enzyme analogs
作者: Li, Jian;  Liu, Yong;  Zhang, Jiang-Wei;  Wei, Hong;  Yang, Ling
刊名: COMPARATIVE MEDICINE
发表日期: 2006-08-01
卷: 56, 期:4, 页:286-290
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Veterinary Sciences ;  Zoology
研究领域[WOS]: Veterinary Sciences ;  Zoology
英文摘要: We 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.
关键词[WOS]: LIVER-MICROSOMES ;  CYTOCHROME-P450 2E1 ;  IN-VITRO ;  IDENTIFICATION ;  DEXTROMETHORPHAN ;  HEPATOCYTES ;  INHIBITORS ;  ISOENZYMES
语种: 英语
WOS记录号: WOS:000240278800008
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/140242
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.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:
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.
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