In vitro and in vivo bimodal effects of docosahexaenoic acid supplements on redox status and platelet function

Abstract : Docosahexaenoic acid (DHA) is a prominent nutrient of marine lipids. Together with eicosapentaenoic acid, it is recognized as a protective molecule against atherosclerosis and thrombosis through the regulation of blood cell functions, especially platelets. Its high unsaturation index may however make it prone to peroxidation, which is usually considered as deleterious. This short review takes into consideration this possibility related to DHA concentrations both in vitro and in vivo. It is suggested that protective effects of DHA on platelet activation depend on the reduction of oxidative stress, and appear bimodal with the abolishment of such a protection when DHA is used at relatively high concentrations. Introduction Docosahexaenoic acid (DHA) is one of the long-chain polyunsaturated fatty acids (PUFA) of the omega-3 family found in marine lipids. Together with eicosapentaenoic acid (EPA), DHA is well-known for its anti-atherothrombotic potential, in particular by decreasing the arachidonic acid (ArA) content of blood cells [1], inhibiting thromboxane production in platelets, as well as leukotriene B4 formation in leukocytes [2]. In addition to these inhibitory effects on ArA metabolism, DHA may decrease athero-thrombogenesis through the action of its lipoxygenase (LOX) end-products. Mono-hydroxylated derivatives produced through 12-, and 15-LOX, namely 11-, 14-, and 17-OH-22:6 (11-, 14-, and 17-HDoHE), respectively, inhibit the thromboxane-induced platelet aggregation (induced by the stable thromboxane A2 receptor agonist U-46619), even stronger than 12-OH-20:4 and-20:5 (12-HETE and-HEPE) [3]. More recently, the double lipoxygenase product of DHA, 10(S),17(S)-diHDoHE, named protectin DX, has been shown to inhibit platelet aggregation through the inhibition of cyclooxygenase-1, which initiates prostanoid synthesis including the potent pro-aggregatory thromboxane A2, as well as the response to the thromboxane A2 mimetic U-46619 [4]. In addition, DHA is known to be oxygenated into several di/tri-OH derivatives (protectin D1, maresins, and resolvins) that are potent inhibitors of the inflammation process [5]. Supplementation of humans with long-chain omega-3 PUFA is usually considered as a positive approach to decrease the risk of atherosclerosis and thrombosis [6], as recently reviewed [7], although some controversies arose in the recent years [8]. Among the controversial issues are the intake doses of those highly unsaturated PUFA, which may be prone to peroxidation [9]. We have been especially interested in the effects of different concentrations of DHA upon blood platelets and their blood environment both in vitro and in vivo, in particular regarding the redox status.
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Prostaglandins, Leukotrienes and Essential Fatty Acids, Elsevier, 2016, Epub ahead of print. 〈10.1016/j.plefa.2016.05.010〉
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Michel Lagarde, Catherine Calzada, Michel Guichardant, Evelyne Véricel. In vitro and in vivo bimodal effects of docosahexaenoic acid supplements on redox status and platelet function. Prostaglandins, Leukotrienes and Essential Fatty Acids, Elsevier, 2016, Epub ahead of print. 〈10.1016/j.plefa.2016.05.010〉. 〈inserm-01299786〉

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