Cytochrome P450 2J2: Potential Role in Drug Metabolism and Cardiotoxicity

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 b...

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Bibliographic Details
Published in:Drug metabolism and disposition 2018-08, Vol.46 (8), p.1053-1065
Main Authors: Solanki, Meetal, Pointon, Amy, Jones, Barry, Herbert, Karl
Format: Article
Language:English
Subjects:
Anticancer properties
Antihistamines
Antitumor agents
Arachidonic acid
Biological effects
Cardiotoxicity
Cardiovascular system
Cytochrome
Cytochrome P450
Cytochromes P450
Drug metabolism
Immunosuppressive agents
Metabolism
Metabolites
Substrates
Vasodilation
Xenobiotics
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Summary: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.
ISSN:0090-9556
1521-009X
DOI:10.1124/dmd.117.078964