title: Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.forename: Sudip
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Sinha
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Calcutta-700054, West Bengal, India. parames@jcbose.ac.in.
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004342:Drug Hypersensitivity; D064420:Drug-Related Side Effects and Adverse Reactions; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System