Fatty acid epoxides in the regulation of the inflammation

Abstract

Cyclooxygenase and lipoxygenase derived lipid metabolites of polyunsaturated fatty acids (PUFAs), as well as their role in the inflammation, have been studied quite thoroughly. However, cytochrome P450 derived lipid mediators, as well as their participation in the regulation of the inflammation, need deeper understanding. In recent years, it has become known that PUFAs are oxidized by cytochrome P450 epoxygenases to epoxy fatty acids, which act as the extremely powerful lipid mediators involved in resolving inflammation. Recent studies have shown that the anti-inflammatory mechanisms of ω-3 PUFAs are also mediated by their conversion to the endocannabinoid epoxides. Thus, it is clear that a number of therapeutically relevant functions of PUFAs are due to their conversion to PUFA epoxides. However, with the participation of cytochrome P450 epoxygenases, not only PUFA epoxides, but also other metabolites are formed. They are further are converted by epoxide hydrolases into pro-inflammatory dihydroxy fatty acids and anti-inflammatory dihydroxyeicosatrienoic acids. The study of the role of PUFA epoxides in the regulation of the inflammation and pharmacological modeling of the activity of epoxide hydrolases are the promising strategies for the treatment of the inflammatory diseases. This review systematizes the current literature data of the fatty acid epoxides, in particular, the endocannabinoid epoxides. Their role in the regulation of inflammation is discussed.