Biological and pathophysiological roles of end-products of DHA oxidation

• Published in: Biochimica et biophysica acta Vol. 1862; no. 4; pp. 407 - 415
• Main Authors: Yakubenko, Valentin P., Byzova, Tatiana V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2017
• Subjects: Animals; Carboxyethylpyrrole; CD36; Diet; Docosahexaenoic acid; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Unsaturated - metabolism; Fish Oils - metabolism; Humans; Inflammation; Inflammation - metabolism; Oxidation-Reduction; Polyunsaturated fatty acids; Randomized Controlled Trials as Topic; Toll-like receptors; HOHA; CPP; Carboxyethylpyrrole; PUFA; HODA; Polyunsaturated fatty acids; CHP; Inflammation; BMDM; EP; Docosahexaenoic acid; CEP; BSA; ROS; HSA; AMD; HOOA; Toll-like receptors; MSA; TLR; CD36; DHA; ELISA
• ISSN: 1388-1981; 1879-2618; 0006-3002; 1879-2618; 1878-2434
• DOI: 10.1016/j.bbalip.2016.09.022

Polyunsaturated fatty acids (PUFA) are known to be present and/or enriched in vegetable and fish oils. Among fatty acids, n-3 PUFA are generally considered to be protective in inflammation-related diseases. The guidelines for substituting saturated fatty acids for PUFAs have been highly publicized for decades by numerous health organizations. Recently, however, the beneficial properties of n-3 PUFA are questioned by detailed analyses of multiple randomized controlled clinical trials. The reported heterogeneity of results is likely due not only to differential effects of PUFAs on various pathological processes in humans, but also to the wide spectrum of PUFA's derived products generated in vivo. The goal of this review is to discuss the studies focused on well-defined end-products of PUFAs oxidation, their generation, presence in various pathological and physiological conditions, their biological activities and known receptors. Carboxyethylpyrrole (CEP), a DHA-derived oxidized product, is especially emphasized due to recent data demonstrating its pathophysiological significance in many inflammation-associated diseases, including atherosclerosis, hyperlipidemia, thrombosis, macular degeneration, and tumor progression. CEP is a product of radical-based oxidation of PUFA that forms adducts with proteins and lipids in blood and tissues, generating new powerful ligands for TLRs and scavenger receptors. The interaction of CEP with these receptors affects inflammatory response, angiogenesis, and wound healing. The detailed understanding of CEP–mediated cellular responses may provide a basis for the development of novel therapeutic strategies and dietary recommendations. •The products of PUFA oxidation exhibit a wide spectrum of biological activities.•CEP, a product of PUFA oxidation, has activities underlying several pathologies.•CEP is endogenous ligand for TLRs and CD36.•CEP-receptor interaction promotes inflammatory cell response.