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Published on: September 25, 2017
Cytochrome P450 2J2: Potential Role in Drug Metabolism and Cardiotoxicity
Meetal Solanki1, Amy Pointon2, Barry Jones2
1Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences, Glenfield Hospital, Leicester (M.S., K.H.), and Safety and ADME Translational Sciences Department, Drug Safety and Metabolism (A.P.), and DMPK, Oncology, IMED Biotech Unit (B.J.), AstraZeneca, Cambridge, United Kingdom mss35@le.ac.uk.
Abstract:
Drug-induced cardiotoxicity may be modulated by endogenous arachidonic acid (AA)-derived metabolites known as epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 2J2 (CYP2J2). The biologic effects of EETs, including their protective effects on inflammation and vasodilation, are diverse because, in part, of their ability to act on a variety of cell types. In addition, CYP2J2 metabolizes both exogenous and endogenous substrates and is involved in phase 1 metabolism of a variety of structurally diverse compounds, including some antihistamines, anticancer agents, and immunosuppressants. This review addresses current understanding of the role of CYP2J2 in the metabolism of xenobiotics and endogenous AA, focusing on the effects on the cardiovascular system. In particular, we have promoted here the hypothesis that CYP2J2 influences drug-induced cardiotoxicity through potentially conflicting effects on the production of protective EETs and the metabolism of drugs.
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