Double lipoxygenation of polyunsaturated fatty acids of nutritional interest.

Double lipoxygenation of polyunsaturated fatty acids having at least three methylene-interrupted double bonds can be made by two lipoxygenases, e.g. 5- and 12-LOX, or 15-LOX only, followed by reduction of the hydroperoxide products through the glutathione peroxidase action.

Biological relevance of double lipoxygenase products of polyunsaturated fatty acids, especially within blood vessels and brain.

The double lipoxygenation of polyunsaturated fatty acids (PUFA) is possible with PUFA having at least three methylene-interrupted double bonds. Several PUFA of the omega-3/n-3 and -6 families may be converted through this route, and the products show interesting inhibitory effects on blood platelet function and cyclooxygenase activities. This review focuses on two main omega-3 PUFA of nutritional interest, namely docosahexaenoic acid (DHA/22:6n-3) and alpha linolenic acid (ALA/18:3n-3).

Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets.

The oxygenation metabolism of arachidonic acid (ArA) has been early described in blood platelets, in particular with its conversion into the potent labile thromboxane A that induces platelet aggregation and vascular smooth muscle cells contraction. In addition, the primary prostaglandins D and E have been mainly reported as inhibitors of platelet function. The platelet 12-lipoxygenase (12-LOX) product, i.

Moderate intake of docosahexaenoic acid raises plasma and platelet vitamin E levels in cystic fibrosis patients.

Patients with cystic fibrosis have increased oxidative stress and impaired antioxidant systems. Moderate intake of docosahexaenoic acid (DHA) may favor the lowering of oxidative stress. In this randomized, double-blind, cross-over study, DHA or placebo capsules, were given daily to 10 patients, 5mg/kg for 2 weeks then 10mg/kg DHA for the next 2 weeks (or placebo).

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

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.

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

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.

Functional fluxolipidomics of polyunsaturated fatty acids and oxygenated metabolites in the blood vessel compartment.

Synthesis of bioactive oxygenated metabolites of polyunsaturated fatty acids and their degradation or transformation products are made through multiple enzyme processes. The kinetics of the enzymes responsible for the different steps are known to be quite diverse, although not precisely determined. The location of the metabolites biosynthesis is diverse as well.

Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients.

Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes.

Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function.

Context: High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D).

Objective: The objective of our study was to investigate the effects of in vitro glycoxidized HDL and HDL from patients with T2D on platelet aggregation and arachidonic acid signaling cascade.

Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity.

Objective: Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed.

Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis.

Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoproteins (LDL). Special focus is given to the effects of marine PUFA on the formation of eicosanoids and docosanoids, and to the bioactive properties of some oxygenated metabolites of omega-3 PUFA produced by cyclooxygenases and lipoxygenases.

Structure-function relationships of non-cyclic dioxygenase products from polyunsaturated fatty acids: poxytrins as a class of bioactive derivatives.

More and more attention is paid to omega-3 fatty acids because of their potential activities in preventing cardiovascular events. In this brief review, we focus on the lipoxygenase end-metabolites of two relevant nutrients belonging to the omega-3 family fatty acids: alpha-linolenic and docosahexaenoic acids, the latter being a prominent component of brain lipids. Dihydroxylated derivatives are described as well as their inhibitory effects on platelet aggregation and cyclooxygenase activities.

Biological properties of a DHA-containing structured phospholipid (AceDoPC) to target the brain.

1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does when present in 1-lyso,2-docosahexaenoyl-GPC (lysoPC-DHA), an efficient DHA transporter to the brain. When incubated with human blood, AceDoPC behaves closer to lysoPC-DHA than PC-DHA in terms of binding to plasma albumin and lipoproteins, and DHA incorporation into platelets and red cells. In addition, AceDoPC prevents more efficiently the deleterious effects of the experimental stroke in rats than does unesterified DHA.

Docosahexaenoic acid, protectin synthesis: relevance against atherothrombogenesis.

DHA is an abundant nutrient from marine lipids: its specific biological effects have been investigated in human volunteers, taking into consideration the dose effects. We report herein that, at dosages below 1 g/d, DHA proved to be effective in lowering blood platelet function and exhibited an 'antioxidant' effect. However, this was no longer the case following 1.

Lipidomics of essential fatty acids and oxygenated metabolites.

Polyunsaturated fatty acids in mammals may be oxygenated into a myriad of bioactive products through di- and monooxygenases, products that are rapidly degraded to control their action. To evaluate the phenotypes of biological systems regarding this wide family of compounds, a lipidomics approach in function of time and compartments would be relevant. The current review takes into consideration most of the diverse oxygenated metabolites of essential fatty acids at large and their immediate degradation products.

Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA.

We have recently described a di-hydroxylated compound called protectin DX (PDX) which derives from docosahexaenoic acid (DHA) by double lipoxygenation. PDX exhibits anti-aggregatory and anti-inflammatory properties, that are also exhibited by similar molecules, called poxytrins, which possess the same E,Z,E conjugated triene geometry, and are synthesized from other polyunsaturated fatty acids with 22 or 20 carbons. Here we present new biological activities of di-hydroxylated metabolites deriving from α-linolenic acid (18:3n-3) treated by soybean 15-lipoxygenase (sLOX).

Inhibitory effects of in vivo oxidized high-density lipoproteins on platelet aggregation: evidence from patients with abetalipoproteinemia.

There is evidence that high-density lipoproteins (HDLs) may regulate platelet function, but disparate results exist regarding the effects of oxidized HDLs on platelets. The objective of our study was to determine the role of in vivo oxidized HDLs on platelet aggregation. Platelet aggregation and redox status were investigated in 5 patients with abetalipoproteinemia (ABLP) or homozygous hypobetalipoproteinemia, two rare metabolic diseases characterized by the absence of apolipoprotein B-containing lipoproteins, compared to 5 control subjects.

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

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 low-density lipoproteins.

Functional lipidomics of oxidized products from polyunsaturated fatty acids.

Because of their high degree of unsaturation, polyunsaturated fatty acids (PUFA) in mammals, with mainly 18, 20 and 22 carbons, can easily be autooxidized, and converted into many oxidized derivatives and degradation products. This short review reports on some of those relevant to the evaluation of oxidative stress in situ. In addition, the enzyme-dependent oxygenation by both dioxygenases and monooxygenases is briefly reviewed by functional and/or metabolic categories, pointing out the structure variety and the analytical approaches.

Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation.

Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown.

DHA metabolism: targeting the brain and lipoxygenation.

Docosahexaenoic acid (DHA), the end-product of the metabolism of omega-3 family fatty acids, is the main polyunsaturated fatty acid of the brain, but its accumulation is incompletely understood. This paper reviews how it could accumulate through specific uptake of DHA-containing lysophosphatidylcholine (LysoPC-DHA). DHA migrates very easily from the sn-2 position of LysoPC, which could be considered as the physiological form of polyunsaturated LysoPC, to the sn-1 position, which is much more stable.

Fatty acid-derived lipid mediators and blood platelet aggregation.

Polyunsaturated fatty acids of nutritional value may affect cell functions after their release from cell lipid storage sites, especially phospholipids, and specific oxygenation by cyclooxygenases, lipoxygenases and cytochrome P(450). The end-products, namely prostanoids, leukotrienes, and mono-, di- and tri-hydroxy derivatives exhibit a variety of biological effects, especially on vascular cells, leukocytes and platelets. This paper reviews some results obtained with blood platelets as target cells, showing that various lipoxygenase end-products, mainly mono- and di-hydroxy derivatives, are inhibitors (IC(50) in microM range) of arachidonic acid-induced aggregation either at the cycloxygenase or thromboxane receptor site level.

Full characterization of PDX, a neuroprotectin/protectin D1 isomer, which inhibits blood platelet aggregation.

Our study aimed to establish the complete structure of the main dihydroxy conjugated triene issued from the lipoxygenation (soybean enzyme) of docosahexaenoic acid, named PDX, an isomer of protectin/neuroprotectin D1 (PD1/NPD1) described by Bazan and Serhan. NMR approaches and other chemical characterization (e.g.

Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men.

Objective: To determine the effect of supplementation with increasing doses of docosahexaenoic acid (DHA), as the only n-3 polyunsaturated fatty acid (PUFA), on low-density lipoprotein (LDL) redox status and oxidizability.

Methods: Twelve healthy men aged 53-65 years ingested consecutive doses of DHA (200, 400, 800 and 1600 mg/day), each dose for two weeks.

Results: The proportions of DHA increased dose-dependently in LDL phospholipids and cholesteryl esters, even after two weeks of supplementation with 200mg/day DHA.

Increasing intakes of the long-chain omega-3 docosahexaenoic acid: effects on platelet functions and redox status in healthy men.

Docosahexaenoic acid (DHA) can prevent cardiovascular events. However, few studies have addressed the effects of DHA on both platelet reactivity and redox status in healthy subjects, and dose-related studies are scarce. The main objectives of the present study were to determine the effects of increasing doses of DHA on platelets and redox status in humans.