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

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journal contribution
posted on 2019-02-04, 11:29 authored by Meetal Solanki, Amy Pointon, Barry Jones, Karl Herbert
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.

Funding

A.P. and B.J. are employees and shareholders of AstraZeneca. M.S. is in receipt of a Biotechnology and Biological Sciences Research Council (BBSRC)–funded PhD CASE award in collaboration with AstraZeneca [Grant BB/M503368/1].

History

Citation

Drug Metabolism and Disposition, 2018, 46 (8), pp. 1053-1065

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Drug Metabolism and Disposition

Publisher

American Society for Pharmacology and Experimental Therapeutics (ASPET)

eissn

1521-009X

Acceptance date

2018-04-19

Copyright date

2018

Available date

2019-02-04

Publisher version

http://dmd.aspetjournals.org/content/46/8/1053

Language

en

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