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首页> 外文期刊>Drug Metabolism and Disposition: The Biological Fate of Chemicals >Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples.
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Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples.

机译:小型猪肝微粒体中细胞色素P450亚型的存在和活性。与人类肝脏样品的比较。

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摘要

Cytochrome P450 (CYP) of the 3A family (CYP3A) has been detected in minipig liver microsomes by immunochemical screening (Western blotting), revealing bands that co-migrate with human CYP3A4 and 3A5. The nifedipine oxidase activity and testosterone 6beta-hydroxylating activity (specific markers for CYP3A enzymes) of the human liver microsomal and minipig liver microsomal samples were comparable, as were the results of specific inhibition of this activity by triacetyloleandomycin. The presence of CYP1A, 2A, 2C, 2D, and 2E1 marker activities in minipig liver microsomes was found by testing with the respective specific substrates (7-ethoxyresorufin, coumarin, tolbutamide, bufuralol, and chlorzoxazone). 7-Pentoxyresorufin O-depentylase activity (indicative of CYP2B) was absent from minipig as well as human liver microsomal samples. The results indicate that minipigs might be, in many cases, the most suitable experimental animals to predict biotransformation pathways in humans, because the activity of the most important CYP isoform in humans (CYP3A, metabolizing the majority of known drug substrates) is present in minipigs, with comparable levels and activities. Moreover, there is no need to induce CYP enzyme levels.
机译:通过免疫化学筛选(Western印迹)在小型猪肝微粒体中检测到3A家族(CYP3A)的细胞色素P450(CYP),揭示了与人CYP3A4和3A5共迁移的条带。人肝微粒体和小型猪肝微粒体样品的硝苯地平氧化酶活性和睾丸激素6β-羟化活性(CYP3A酶的特定标记)具有可比性,三乙酰油霉素对这种活性的特异性抑制结果也相当。通过用各自的特定底物(7-乙氧基间苯三酚,香豆素,甲苯磺丁酰胺,布氟洛尔和氯唑沙宗)进行测试,发现小型猪肝微粒体中存在CYP1A,2A,2C,2D和2E1标记活性。小型猪以及人肝微粒体样品中均没有7-Pentoxyresorufin O-去戊基酶活性(指示CYP2B)。结果表明,在许多情况下,小型猪可能是预测人类生物转化途径的最合适的实验动物,因为小型猪中存在人类中最重要的CYP亚型(CYP3A,可代谢大多数已知的药物底物)的活性。 ,具有可比的水平和活动。而且,不需要诱导CYP酶水平。

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