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Developmental changes in drug-metabolizing enzyme expression during metamorphosis of Xenopus tropicalis

机译:异常杂志性能酶促药物代谢酶表达的发育变化

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A large number of chemicals are routinely detected in aquatic environments, and these chemicals may adversely affect aquatic organisms. Accurate risk assessment requires understanding drug metabolizing systems in aquatic organisms because metabolism of these chemicals is a critical determinant of chemical bioaccumulation and related toxicity. In this study, we evaluated mRNA expression levels of nuclear receptors and drug-metabolizing enzymes as well as cytochrome P450 (CYP) activities in pro-metamorphic tadpoles, froglets, and adult frogs to determine how drug-metabolizing systems are altered at different life stages. We found that drug-metabolizing systems in tadpoles were entirely immature, and therefore, tadpoles appeared to be more susceptible to chemicals compared with metamorphosed frogs. On the other hand, cypla mRNA expression and CYP1A-like activity were higher in tadpoles. We found that thyroid hormone (TH), which increases during metamorphosis, induced CYP1A-like activity. Because endogenous TH concentration is significantly increased during metamorphosis, endogenous TH would induce CYP1A-like activity in tadpoles.
机译:在水生环境中常规检测到大量化学品,这些化学品可能会对水生生物产生不利影响。准确的风险评估需要了解水生生物中药物代谢系统,因为这些化学品的代谢是化学生物累积和相关毒性的关键决定因素。在该研究中,我们评估了核受体和药物代谢酶的mRNA表达水平以及在促多晶蝌蚪,骨肉和成人青蛙中的细胞色素P450(CYP)活性,以确定药物代谢系统如何在不同的寿命中改变。我们发现蝌蚪的药物代谢系统完全不成熟,因此,与变质青蛙相比,蝌蚪与化学品更容易受到影响。另一方面,蝌蚪的Cypla mRNA表达和CYP1A样活性较高。我们发现甲状腺激素(TH),在变态期间增加,诱导CYP1A样活动。由于在变态期间内源性浓度显着增加,所以内源性TH将在蝌蚪中诱导CYP1A样活性。

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