Cytochrome P450s: Mechanisms and Biological Implications in Drug Metabolism and its Interaction with Oxidative Stress

Author(s): Sudip Bhattacharyya, Krishnendu Sinha, Parames C. Sil.

Journal Name: Current Drug Metabolism

Volume 15 , Issue 7 , 2014


Abstract:

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.

Keywords: Bimodal signals, Cytochrome P450, drug metabolism, drug toxicity, mitochondria, oxidative stress, pathophysiology, reactive metabolites.

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Article Details

VOLUME: 15
ISSUE: 7
Year: 2014
Page: [719 - 742]
Pages: 24
DOI: 10.2174/1389200215666141125121659
Price: $58

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