Dose-effect and metabolism of docosahexaenoic acid: Pathophysiological relevance in blood platelets

Abstract

Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood components, especially platelets, will be reviewed here. Investigating the dose-effect of DHA in humans shows that daily intake lower than one gram/day brings several benefits, such as inhibition of platelet aggregation, resistance of monocytes against apoptosis, and reinforced antioxidant status in platelets and lowdensity lipoproteins. However, higher daily intake may be less efficient on those parameters, especially by losing the antioxidant effect. On the other hand, a focus on the inhibition of platelet aggregation by lipoxygenase end-products of DHA is made. The easy conversion of DHA by lipoxygenases and the formation of a double lipoxygenation product named protectin DX, reveal an original way for DHA to contribute in platelet inhibition through both the cyclooxygenase inhibition and the antagonism of thromboxane A 2 action.

Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype

“…PDX is a newly identified di-oxygenated derivatives from DHA, it can be produced by human neutrophils incubated with DHA and can be found together with PD1 in inflammatory exudates 12 . PDX was shown to inhibit platelet aggregation and neutrophil activation by blocking cyclooxygenase-1 (COX-1) and COX-2 as well as antagonizing TxA2 receptor 8, 10 . In addition to its isomer PD1, PDX 32 (mistaken as PD1 throughout the paper) inhibited the replication of influenza virus and conferred protection against the infectious disease.…”

“…PDX (10S, 17S-dihydroxy-docosa-4Z, 7Z, 11E, 13Z, 15E, 19Z-hexaenoic acid) is a new lipid mediator derived from DHA by double lipoxygenation and is an isomer of protectin D1 (PD1, 10R, 17S-dihydroxydocosa-4Z, 7Z, 11E, 13E, 15Z, 19Z-hexaenoic acid), both of them can be found in DHA challenged neutrophils or inflammatory exudates 8, 9 . PDX not only displayed the classic function of protectins in the process of inflammation resolution but also exhibited anti-aggregatory property in human neutrophil 10–12 .…”

Marine microalgae used as food supplements and their implication in preventing cardiovascular diseases

“…The high amounts of EPA in this microalga could explain the crucial role of this fatty acid in reducing platelet aggregability (Lagarde et al, 2013). Concerning the oxidative stress parameters, it has been reported lower MDA levels and increased GPx activity in the liver after consumption of O. aurita, in high fat fed rats.…”

Comparison of docosahexaenoic acid uptake in murine cardiomyocyte culture and tissue: Significance to physiologically relevant studies

“…the formation of protectins [26] and the inhibition of reactive oxygen species generation and diffusion [18], can also play roles in the prevention and resolution of inflammatory damage. In addition, we did not explore and, therefore, cannot rule out the possibility that DHA inhibits cardiomyocytic COX, as reported in endothelial cells [27] and platelets [28].…”