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Molecular clock mechanisms of drug metabolism

机译:药物代谢的分子钟机制

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Acetaminophen (APAP) is a widely used analgesic drug and is mainly biotransfor-med and eliminated as nontoxic conjugates with glucuronic acid and sulfate. In the present study, the 24-hr rhythm of metabolism such as GSH conjugation and cyto-chrome P-450 (CYP) 2E1 is responsible for that of hepatotoxicity induced by APAP. Transcription of the CYP2E1 promoter was rhythmically enhanced by hepatic nuclear factor-1alpha (HNF-1alpha), and CRY1 rhythmically inhibited CYP2E1 promoter activation by HNF-1alpha. Metabolism by CYP is common metabolic pathways for many drugs. The monitoring of rhythmic markers such as clock genes may be useful in choosing the most appropriate time of day for administration of drugs and may increase their therapeutic effects and/or reduce their side effects.
机译:乙酰氨基酚(APAP)是一种广泛使用的镇痛药,主要是生物转移 - MED,并以葡糖和硫酸盐作为无毒缀合物。在本研究中,代谢如GSH缀合和细胞铬P-450(CYP)2E1的24-HR节奏是由APAP诱导的肝毒性的负责。通过肝核因子-1Alpha(HNF-1Alpha)对CYP2E1启动子的转录进行有节奏地增强,CRY1有节奏抑制的CYP2E1启动子激活HNF-1α。 CYP的新陈代谢是许多药物的常见代谢途径。监测诸如时钟基因的节奏标记物可用于选择药物施用的最合适的时间,并且可以增加其治疗效果和/或降低副作用。

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