Cytochrome P450 enzymes and the heart

Abstract

SummaryThe cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of heme-thiolate enzymes, which are important in the metabolism of foreign and endogenous compounds. Genetic variations, drug interactions, or pathophysiological factors can lead to reduced, absent, or increased enzymatic activity. This altered CYP activity greatly influences an individual's response to therapeutic treatment. What is not known is the impact of these changes on the many functional roles of CYP in physiological and pathophysiological processes of the heart. Many extrahepatic tissues, like heart, contain active P450 enzymes but lack information regarding their role in cellular injury or homeostasis. Much of our current knowledge about cardiac CYP has been limited to studies investigating the role of fatty acid metabolites in heart. Traditional risk factors including diabetes, smoking, and hypertension have well established links to cardiovascular disease. And new evidence strongly suggests exposure to chemicals and other environmental agents has a profound impact on the cardiovascular system. These risk factors can independently affect the expression and activity of CYP enzymes. Therefore, altered CYP activity is important from a detoxification as well as a bioactivation perspective. Considering CYP, interactions are greatly dependent on inherited differences or acquired changes in enzyme activity further research into their potential impact on pathogenesis, risk assessment, and therapy of heart disease is warranted. This review explores the expression of CYP isoforms, their functional roles, and the effects of genetic variation in the heart.

Anti-inflammatory ω-3 endocannabinoid epoxides

“…Human CYP2J2 epoxygenates AEA and 2-arachidonoylglycerol (2-AG) (28) and is physiologically relevant, because it is the second most highly expressed P450 in the human brain (29) and is the most highly expressed P450 in human cardiomyocytes (30). However, the cross-species studies are not completely translatable, because BV-2 microglial cells are derived from mice, which have 10 subfamily CYP2J isozymes (CYP2J-5, -6, -7, -8, -9, -11, -12, -13, -14, -15) but lack a comparable CYP2J2 isozyme, making comparative species studies more difficult (31).…”

Targeted label-free approach for quantification of epoxide hydrolase and glutathione transferases in microsomes

“…48 Sometimes the metabolism of xenobiotics can produce toxic 49 metabolites, some of which have been implicated in tumor initiation 50 and progression. Although liver is the major organ possessing the 51 largest metabolic capacity, CYP450s are also present in extrahepatic 52 tissues including kidney [1], lung [2], heart [3], brain [4], small intes-53 tine [5], and skin [6]. The presence of drug-metabolism enzymes 54 (DMEs) in extrahepatic tissues indicates that different organs may 55 also be involved in the general metabolism of xenobiotics.…”

Beneficial Effects of Ethanolic Leaf Extract of Coriandrum Sativum on Metanil Yellow Induced Alteration Inactivity of Catalase and Level of Lipid Peroxidation in Hercine Cardiac Tissue in Vitro

“…Metanil yellow, when administered in single dose parenterally, induces P-450 and its dependent monooxygenases which is related it's to hepatic metabolism and toxicity [27]. P-450 dependent monooxygenase is also adequate in the heart.…”