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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
刊名COMPARATIVE MEDICINE
2006-08-01
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
关键词[WOS]LIVER-MICROSOMES ; CYTOCHROME-P450 2E1 ; IN-VITRO ; IDENTIFICATION ; DEXTROMETHORPHAN ; HEPATOCYTES ; INHIBITORS ; ISOENZYMES
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.
语种英语
WOS记录号WOS:000240278800008
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/140242
专题中国科学院大连化学物理研究所
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
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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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