Cytochrome P450s: Mechanisms and Biological Implications in Drug Metabolism and its Interaction with Oxidative Stress
Cytochrome P450s: Mechanisms and Biological Implications in Drug Metabolism and its Interaction with Oxidative Stress
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DOI：
10.2174/1389200215666141125121659
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发表时间：
2014-01-01
影响因子：
2.3
通讯作者：
Sil, Parames C.
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Sudip;Sinha, Krishnendu;Sil, Parames C.
背景资料：细胞色素单加氧酶P450是一类末端氧化酶，属于多基因血红素巯基化酶家族，分布于内质网、细胞质和线粒体的多个位点。CYP在药物代谢中起催化剂的作用，主要内容包括：线粒体和微粒体CYP的代谢功能，CYP介导的ROS产生及其反馈，药物的生物活化和相关的超敏反应，代谢处置以及药物的治疗方法。几乎所有的药物在高剂量或意外过量时都会出现一些不良反应。药物引起超敏反应，而药物超敏反应的代谢易感性又加重了药物超敏反应，主要是CYP介导的药物代谢的不同中间活性产物。另一方面，CYP是ROS的主要来源。它们的产生和反馈是本次审查的主要关注点。除了药物代谢外，CYP也对致癌物代谢有重要作用。最终，药物代谢和抗氧化治疗中的其他酶是不可或缺的。该领域的重要性：从全球意义上讲，了解确切的机制可以促进制药行业开发无毒药物的挑战。本文就CYP介导药物代谢的分子机制和复杂的交叉作用机制作一综述。各种恢复性的新策略之间的会谈由CYP进化来维持氧化还原平衡和限制氧化应激的来源。
Background: Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism.Areas covered: This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches.What the readers will gain: CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible.Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity.Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.