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首页> 外文期刊>Biomolecules & therapeutics >Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay
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Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay

机译：基于美沙拉嗪和枸s酸莫沙必利的发光测定法测定人细胞色素P450酶的诱导

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Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that GYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure GYP induction, we determined CYP induction by using luminescent assay. Luminescent GYP assays link GYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of GYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent GYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent GYP assays decrease the interference between the optical properties of the test compound and the GYP substrates. Therefore, luminescent GYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput GYP screening during early drug discovery.
机译：药物代谢主要发生在肝脏中。细胞色素P450（CYP）是一种药物代谢酶，负责许多重要的药物代谢反应。最近，美国FDA和EU EMA建议可以通过酶活性和mRNA表达来测量GYP酶的诱导。但是，这些实验很耗时，而且它们的分析间差异可能导致对结果的误解。为了解决这些问题并建立一种更强大的方法来测量GYP诱导，我们通过使用发光测定法确定了CYP诱导。发光GYP分析将GYP酶活性与萤火虫荧光素酶发光技术联系起来。在这项研究中，我们使用光度计测量了冷冻保存的人肝细胞（HMC424、478和493）中GYP同工酶（1A2、2B6、2C9和3A4）的诱导。然后，我们检查了美沙拉嗪（一种用于结肠炎的药物）和柠檬酸莫沙必利（用作抗痉挛药）的潜在诱导能力（迄今为止未知）。结果显示美沙拉嗪可促进CYP2B6和3A4活性，而莫沙必利柠檬酸盐可促进CYP1A2、2B6和3A4活性。与LC-MS / MS和qRT-PCR方法相比，发光GYP分析具有快速安全的优势。此外，发光GYP分析降低了测试化合物和GYP底物的光学性质之间的干扰。因此，发光GYP分析的劳动强度小，速度快，并且可以用作早期药物开发过程中高通量GYP筛选的强大工具。

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