Drug metabolism and cytochrome P-450 (CYPs)

Blnd Mohammed, K. Dizaye, Bushra Amin
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Abstract

Cytochrome p-450 (CYPs) convert xenobiotics, chemicals, and drugs in the liver into intoxic materials that can be easily eliminated in the body. However, these CYPs sometimes mediate fatal diseases by converting drugs (for instance, paracetamol) into toxic substances that cannot be eliminated or excreted quickly from the body and hence cause hepatocyte damage that decreases the function of the liver. This article review aimed to determine the history, nomenclature, family, and subfamily of CYPs and mainly stress cytochrome P450 roles in drug metabolism. Some toxic byproducts induce autoreactive antibodies by binding to the CYPs, which causes further damage to hepatocytes. The most common causes of liver damage are type II autoimmune hepatitis, drinking alcohol, and free radicals, which cause DNA mutations. Another condition that leads to liver damage is the inability of the liver to detoxify the drug, which leads to further damage to the liver. There are some isoforms of CYPs, such as 3A, 1A, and 2C19, that are severely affected when the liver is no longer able to relieve toxic products, but some isoforms of CYPs are less affected during damage to the liver, which includes 2E1, 2D6, and 2C9. There are parameters for the involvement of CYPs in liver disease, depending on the cause of the damage, which is either drugs or alcohol. Thus, further research must be done to know the exact etiology and management of the diseases related to liver damage through CYPs.
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药物代谢与细胞色素 P-450 (CYPs)
细胞色素 p-450 (CYPs) 在肝脏中将异种生物、化学物质和药物转化为易于在体内排出的有毒物质。然而,这些细胞色素 p-450 有时也会将药物(如扑热息痛)转化为有毒物质,无法迅速排出体外,从而导致肝细胞损伤,降低肝脏功能,从而引发致命疾病。本文综述了 CYPs 的历史、命名、家族和亚家族,主要强调细胞色素 P450 在药物代谢中的作用。一些有毒副产品会通过与 CYPs 结合诱发自反应抗体,从而对肝细胞造成进一步损害。造成肝损伤的最常见原因是 II 型自身免疫性肝炎、饮酒和导致 DNA 变异的自由基。另一种导致肝损伤的情况是肝脏无法解毒,从而导致肝脏进一步受损。有一些 CYPs 同工酶,如 3A、1A 和 2C19,在肝脏无法再解除有毒产物时会受到严重影响,但有些 CYPs 同工酶在肝脏受损时受影响较小,其中包括 2E1、2D6 和 2C9。CYPs参与肝病的参数取决于损害的原因,即药物或酒精。因此,必须开展进一步的研究,以了解与通过 CYPs 造成肝损伤有关的疾病的确切病因和治疗方法。
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审稿时长
24 weeks
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