Omega-3 Polyunsaturated Acids Research Articles

Atherogenic features of the fatty acid profile of erythrocyte membranes of patients with fatty liver disease of mixed genesis

Aim of the study was to investigate the features of the fatty acid (FA) profile of erythrocyte membranes of patients with fatty liver disease (FLD) of mixed genesis (metabolic + alcoholic) from the point of view of atherogenic changes.Material and methods. 31 men (50.6 ± 9.9 years old) with FLD of mixed genesis, the degree of liver fibrosis corresponded to 0-1 (FibroScan ® 502 Echosens, France), and 28 persons of the comparison group, comparable in age, were examined. The study of the composition of FAs of erythrocyte membranes was carried out using gas chromatography/mass spectrometry – a system based on three quadrupoles Agilent 7000B (USA).Results. Patients with FLD of mixed genesis had higher level of palmitoleic (p = 0.03), pentadecanoic (p = 0.05), omega-6 to omega-3 polyunsaturated fatter acids (PUFA) ratio (p = 0.03) and, conversely, lower level of docosahexaenoic (p = 0.0002), total content of eicosapentaenoic and docosahexaenoic FA (p = 0.0007), of all omega-3 PUFA (p = 0.001) in the membranes of erythrocytes compared to healthy persons. There are trends towards a decrease in the content of omega-3 eicosapentaenoic acid and an increase in the ratio of SFA/PUFA in patients with fibroids of mixed genesis in contrast to healthy individuals. The level of individual FA provided high diagnostic accuracy in differentiating patients with FLD of mixed genesis from healthy individuals: palmitoleic (9-C16:1) (area under ROC (AUC) 0.702, sensitivity 66.7 %, specificity 69.6 %), docosahexaenoic (C22:6n-3) (AUC 0.795, sensitivity 77.3 %, specificity 78.3 %), as well as the total content of eicosapentaenoic and docosegexaenoic FA (C20:5n-3 + C22:6n-3) (AUC 0.777, sensitivity 70.1 %, specificity 82.6 %).Conclusions. The revealed features of the profile of erythrocyte membrane FA in FLD of mixed genesis – increase of saturated, monounsaturated, omega-6 PUFA content and reduce of omega-3 PUFA concentration are atherogenic. The continuation of research in terms of the use of FAs as biomarkers of this pathology and targets for therapeutic effects should be considered promising.

Полуконсервы рыбной паштетной группы с иммуномодулирующими компонентами

In accordance with the Strategy for improving the quality of food products in the Russian Federation until 2030, the priority is scientific research in the field of nutrition of the population, including in the field of prevention of the most common non-infectious diseases and the development of production technologies aimed at improving the quality of food products, as well as promoting the principles of healthy nutrition. One of the ways to increase and promote them is the development of products containing immunomodulating components, which refers to promising areas for strengthening the immune defense of the human body. There are presented the formulations of finished food products (fish pates) containing components with immunomodulatory properties, such as fat-soluble vitamins A and D, Omega-3 polyunsaturated acids, copper (Cu) and the prebiotic inulin. Optimal formulations have been designed and the technology of the products has been developed. Analyses of the quality indicators of the developed finished products allowed us to establish its high nutritional, in particular biological value: semi-canned food contains fat-soluble vitamins A (386.50 - 443.31 mcg/100 g) and D (10.39 - 12.96 mcg/100 g), polyunsaturated fatty acids of the Omega-3 group (1.02 g - 1.35 g), essential microelement copper (0.86 - 1.21 mg/100 g), as well as dietary fibers, in particular inulin (3.12 - 3.49%), the amount of which will satisfy the daily physiological need by more than 15%, which allows to recommend them as natural functional food products with immunomodulating components.

The Effects of Omega-3 Supplementation on Resting Metabolic Rate: A Systematic Review and Meta-Analysis of Clinical Trials.

Background It is uncertain if omega-3 polyunsaturated fatty acids are associated with increase in resting metabolic rate (RMR) in adults. Objective The aim of the present study was to evaluate the overall effects of omega-3 on RMR. Methods Both PubMed and Scopus libraries were searched up to April 2021. Study quality was assessed using the Jadad scale. Random- and fixed-effects models were utilized in order to obtain pooled estimates of omega-3 supplementation impacts on RMR, using weight mean difference (WMD). Results Seven studies including a total of 245 participants were included. There was significantly higher FFM-adjusted RMR in the intervention group than the control group (WMD: 26.666 kcal/kg/day, 95% CI: 9.010 to 44.322, p=0.003). Study quality showed that four of seven included studies were of high quality. However, there was no significant difference in results in the subgroup analysis according to the quality of studies. Subgroup analyses revealed significant changes for sex (for women: WMD = 151.793 kcal/day, 95% CI = 62.249 to 241.337, p=0.001) and BMI (for BMI > 25: WMD = 82.208 kcal/day, 95% CI = 0.937 to 163.480, p=0.047). Influence analysis indicated no outlier among inclusions. Conclusion The current study depicted that omega-3 polyunsaturated acids can significantly increase RMR in adults. However, further assessments of omega-3 supplementation therapy are critical to monitor its long-term outcomes and potential clinical application.

Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease.

Fibrates and omega-3 polyunsaturated acids are used for the treatment of hypertriglyceridemia but have not demonstrated consistent effects on cardiovascular (CV) risk. In this study, we investigate how these two pharmacological agents influence plasma levels of bioactive lipid mediators, aiming to explore their efficacy beyond that of lipid-lowering agents. Plasma from overweight patients with non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200mg or 4g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides. OM-3CA reduced plasma concentrations of proinflammatory PGE2 , as well as PGE1 , PGD1 and thromboxane B2 but increased prostacyclin, and eicosapentaenoic acid- and docosahexaenoic acid-derived lipids of lipoxygenase and cytochrome P450 monooxygenase (CYP) (e.g., 17-HDHA, 18-HEPE, 19,20-DiHDPA). Fenofibrate reduced plasma concentrations of vasoactive CYP-derived eicosanoids (DHETs). Although OM-3CA increased plasma levels of the NAE docosahexaenoyl ethanolamine and docosapentaenoyl ethanolamine, and fenofibrate increased palmitoleoyl ethanolamine, the effect of both treatments may have been masked by the placebo (olive oil). Fenofibrate was more efficacious than OM-3CA in significantly reducing plasma ceramides, pro-inflammatory lipids associated with CV disease risk. Neither treatment affected putative lipid species associated with NAFLD. Our results show that OM-3CA and fenofibrate differentially modulate the plasma mediator lipidome, with OM-3CA promoting the formation of lipid mediators with potential effects on chronic inflammation, while fenofibrate mainly reducing ceramides. These findings suggest that both treatments could ameliorate chronic inflammation with possible impact on disease outcomes, independent of triglyceride reduction.

Eicosapentaenoic acid supplemented to in vitro maturation medium results in lesser lipid content and intracellular reactive oxygen species in blastocysts of cattle

Sub-optimal cattle embryo development to the blastocyst stage still is a problem when conducting in vitro production (IVP) procedures. Supplementation of in vitro maturation (IVM) medium with omega 3-polyunsaturated eicosapentaenoic acid (EPA) is an approach that might have positive effects on lipid metabolism of cattle oocytes, potentially improving subsequent embryo development. The aim of this study was to evaluate effects of EPA addition to serum-free IVM medium on pronuclear formation after in vitro fertilization, cleavage, and blastocyst rates. Effects of EPA on lipid accumulation and intracellular reactive oxygen species (ROS) generation with IVP of cattle embryos was also investigated. In all experiments, cumulus-oocyte complexes were matured in IVM medium supplemented with 0 nM, 1 nM, or 1 μM EPA for 24 h. Pronuclear formation, cleavage, and blastocyst rates were similar for embryos when there was supplementation of EPA at all concentrations to those of the control group (P > 0.05). The inclusion of 1 nM EPA in medium resulted in a greater lipid content and less intracellular ROS in day 8-embryos compared with those of the Control group (P < 0.05). There were no differences, however, when there was inclusion of 1 μM EPA compared to embryos of the Control group at the day 8 developmental stage (P > 0.05). In conclusion, supplementation with IVM medium with the 1 nM EPA concentration resulted in a lesser blastocyst lipid and intracellular ROS concentration, without modifying embryo development, therefore, EPA could be a desirable supplement to improve embryo quality in cattle.

Morphology of rat brain neurons in subtotal ischaemia and introduction of L-NAME and omega-3 polyunsaturated fatty acids

Introduction. Cerebral ischaemia leads to the development of numerous morphofunctional disorders of the cerebral cortex, which can be exacerbated by the introduction of a Nω-nitro-L-arginine methyl ester (L-NAME), which is a non-selective inhibitor of nitric oxide synthase (NOS). Aim. To study the morphological features of rat brain neurons in subtotal ischaemia during the administration of L-NAME and naturally occurring omega-3 polyunsaturated docosahexaenoic acid (DHA). Material and Methods. Subtotal cerebral ischaemia was modelled in rats by ligation of both common carotid arteries. L-NAME and DHA were given individually or in combination to separate groups of rats. L-NAME (5 mg/kg) was administered intramuscularly immediately before ligation and DHA (5 mg/kg) intragastrically during the week before ligation. Results. The introduction of DHA alone had a corrective effect on the hippocampus under conditions of subtotal ischaemia, reducing the number of shadow cells and hyperchromic wrinkled neurons, without significantly affecting the size and shape of the neurons of the parietal cortex. However, the previous administration of DHA to rats with cerebral ischaemia receiving a NOS inhibitor did not abrogate the negative effects on the state of the neurons in the cerebral cortex. Conclusion. The administration of DHA can modulate the morphological disorder of the hippocampus which occurs in subtotal cerebral ischaemia.

Marine Protists and Rhodotorula Yeast as Bio-Convertors of Marine Waste into Nutrient-Rich Deposits for Mangrove Ecosystems

This paper represents a comprehensive study of two new thraustochytrids and a marine Rhodotorula red yeast isolated from Australian coastal waters for their abilities to be a potential renewable feedstock for the nutraceutical, food, fishery and bioenergy industries. Mixotrophic growth of these species was assessed in the presence of different carbon sources: glycerol, glucose, fructose, galactose, xylose, and sucrose, starch, cellulose, malt extract, and potato peels. Up to 14g DW/L (4.6gDW/L-day and 2.8gDW/L-day) of biomass were produced by Aurantiochytrium and Thraustochytrium species, respectively. Thraustochytrids biomass contained up to 33% DW of lipids, rich in omega-3 polyunsaturated docosahexaenoic acid (C22:6, 124mg/g DW); up to 10.2mg/gDW of squalene and up to 61μg/gDW of total carotenoids, composed of astaxanthin, canthaxanthin, echinenone, and β-carotene. Along with the accumulation of these added-value chemicals in biomass, thraustochytrid representatives showed the ability to secrete extracellular polysaccharide matrixes containing lipids and proteins. Rhodotorula sp lipids (26% DW) were enriched in palmitic acid (C16:0, 18mg/gDW) and oleic acid (C18:1, 41mg/gDW). Carotenoids (87μg/gDW) were mainly represented by β-carotene (up to 54μg/gDW). Efficient growth on organic and inorganic sources of carbon and nitrogen from natural and anthropogenic wastewater pollutants along with intracellular and extracellular production of valuable nutrients makes the production of valuable chemicals from isolated species economical and sustainable.

Ключевые микронутриенты репродуктивного периода – фолаты и докозагексаеновая омега-3 полиненасыщенная жирная кислота – в профилактике перинатальной депрессии

Ключевые микронутриенты репродуктивного периода – фолаты и докозагексаеновая омега-3 полиненасыщенная жирная кислота – в профилактике перинатальной депрессии

Characterisation of the vasodilation effects of DHA and EPA, n-3 PUFAs (fish oils), in rat aorta and mesenteric resistance arteries.

Background and purposeIncreasing evidence suggests that the omega-3 polyunsaturated acids (n-3 PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are beneficial to cardiovascular health, promoting relaxation of vascular smooth muscle cells and vasodilation. Numerous studies have attempted to study these responses, but to date there has not been a systematic characterisation of both DHA and EPA mediated vasodilation in conduit and resistance arteries. Therefore, we aimed to fully characterise the n-3 PUFA-induced vasodilation pathways in rat aorta and mesenteric artery.MethodsWire myography was used to measure the vasomotor responses of freshly dissected rat mesenteric artery and aorta. Arteries were pre-constricted with U46619 and cumulative concentrations of either DHA or EPA (10 nM-30 μM) were added. The mechanisms by which n-3 PUFA relaxed arteries were investigated using inhibitors of vasodilator pathways, which include: nitric oxide synthase (NOS; L-NAME), cycloxygenase (COX; indomethacin), cytochrome P450 epoxygenase (CYP450; clotrimazole); and calcium-activated potassium channels (KCa), SKCa (apamin), IKCa (TRAM-34) and BKCa (paxilline).ResultsBoth DHA- and EPA-induced relaxations were partially inhibited following endothelium removal in rat mesenteric arteries. Similarly, in aorta EPA-induced relaxation was partially suppressed due to endothelium removal. CYP450 also contributed to EPA-induced relaxation in mesenteric artery. Inhibition of IKCa partially attenuated DHA-induced relaxation in aorta and mesenteric artery along with EPA-induced relaxation in mesenteric artery. Furthermore, this inhibition of DHA- and EPA-induced relaxation was increased following the additional blockade of BKCa in these arteries.ConclusionsThis study provides evidence of heterogeneity in the vasodilation mechanisms of DHA and EPA in different vascular beds. Our data also demonstrates that endothelium removal has little effect on relaxations produced by either PUFA. We demonstrate IKCa and BKCa are involved in DHA-induced relaxation in rat aorta and mesenteric artery; and EPA-induced relaxation in rat mesenteric artery only. CYP450 derived metabolites of EPA may also be involved in BKCa dependent relaxation. To our knowledge this is the first study indicating the involvement of IKCa in n-3 PUFA mediated relaxation.

Leptin alone and in combination with interleukin-1-beta induced cartilage degradation potentially inhibited by EPA and DHA

ABSTRACTOsteoarthritis (OA) is the most common form of arthritis. Obesity has been believed to be an important risk factor for OA development and the progression of not only load-bearing joints, but low-load-bearing joints as well. Increased leptin has been the focus of a link between obesity and OA. In this study, the effects of pathological (100ng/ml) or supra-pathological (10μg/ml) concentrations of leptin alone or in combination with IL1β on cartilage metabolisms were studied in porcine cartilage explant. The involved mechanisms were examined in human articular chondrocytes (HACs). Moreover, the protective effect of omega-3 polyunsaturated acids, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was also investigated. Leptin (10μg/ml) alone or in combination with IL1β could induce cartilage destruction, although lower concentrations had no effect. Leptin activated NFκB, ERK, JNK and p38 in HACs, which led to the induction of MMP3, MMP13 and ADAMTS4 secretions. The combined effect could further induce those enzymes through the additive effect on activation of NFκB and JNK. Interestingly, both EPA and DHA could inhibit cartilage damage induced by leptin plus IL1β by reducing the activation of NFκB and JNK, which led to the decrease of ADAMTS4 secretion. Altogether, only a supra-pathological concentration of leptin alone or in combination with IL1β could induce cartilage destruction, whereas a pathological one could not. This effect could be inhibited by EPA and DHA. To gain greater understanding of the link between leptin and OA, the effect of different levels of leptin on several states of OA cartilage requires further investigation.

P.1.b.006 - Investigation of long-term potentiation in young and old hyperthyroid rats

Docosahexaenoic acid (DHA) is a 22 carbon, six cis-double bonded (22:6, w3) omega-3 polyunsaturated acid (PUFA), found highly enriched with neuronal membranes, and believed to play a critical role in synaptic plasticity and cognitive correlates of learning and memory. DHA is released from the neuronal membrane via the action of the cytostolic calcium-independent phospholipase A2 (iPLA2) enzyme. Previous studies have demonstrated that inhibition of iPLA2 by bromoenol lactone (BEL), results in inhibition of CA1 long-term potentiation (LTP), restored following acute application of DHA. In the present study, we investigated the effect of selective iPLA2 inhibition and acute application of DHA on corticostriatal synaptic plasticity. We demonstrate that acute application of 30 μM DHA facilitates cotricostriatal LTP, whilst long-term depression (LTD), basal transmission, and paired-pulse facilitation (PPF) are unaffected. Conversely, selective inhibition of iPLA2, via acute application of 10 μM BEL, inhibits the expression of corticostriatal LTP, with no effect on LTD. Furthermore, we show that 10 μM BEL inhibition of LTP is reversed following acute application of 30 μM DHA. Finally, we demonstrate that 10 μM BEL inhibits depotentiation of corticostriatal LTP, which is restored following acute application of 30 μM DHA. Our findings indicate that appropriate release of DHA is a critical facet of corticostriatal LTP and depotentiation, and thus provides an exciting cellular target for the positive facilitation of cognitive function observed following DHA dietary supplementation.

Docosahexaenoic Acid Attenuates Doxorubicin-induced Cytotoxicity and Inflammation by Suppressing NF-κB/iNOS/NO Signaling Pathway Activation in H9C2 Cardiac Cells.

Doxorubicin (DOX) is a widely used antineoplastic agent for a variety of carcinomas. However, it is cardiotoxic and leads to cardiomyopathy. Previous studies have indicated that omega-3 polyunsaturated acids (ω-3 PUFAs) have therapeutic effects on dilated and diabetic cardiomyopathies. However, whether ω-3 PUFAs exert therapeutic effects on DOX-induced cardiomyopathy remains unclear. In this study, we explored the effect and underlying mechanisms of docosahexaenoic acid (DHA), an important type of ω-3 PUFA, on DOX-induced cardiotoxicity and inflammation. H9C2 cardiac cells were exposed to DOX (5 μM) and interfered with by DHA (10 μM) for 4 hours. The effect of DHA on H9C2 cell viability was measured by Cell Counting Kit-8 assay. The levels of mRNA and protein expression of inflammatory cytokines were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Reactive oxygen species and nitric oxide (NO) levels were determined by corresponding kits. The protein expression of key molecules in the nuclear factor-kappa B/inducible isoform of nitric oxide synthase/nitric oxide (NF-κB/iNOS/NO) signaling pathway was determined by western blotting. DOX-induced significant cytotoxicity and reactive oxygen species production in H9C2 cardiac cells. It also induced cardiac inflammation as evidenced by significantly increased expressions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1β, monocyte chemoattractant protein-1, and inducible isoform of NO synthase. However, DHA effectively attenuated DOX-induced cytotoxicity and inflammation. A further mechanistic study revealed that DHA suppressed DOX-induced activation of the NF-κB/iNOS/NO signaling pathway in H9C2 cells. Our results indicate that DHA may protect against DOX-induced cardiotoxicity by inhibiting NF-κB/iNOS/NO signaling pathway activation.

Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by Combining Omega-3 Polyunsaturated Acid with Lyciumbarbarum Polysaccharide.

Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons using an in vitro ischemic model. Our study demonstrated that treatment with docosahexaenoic acid (DHA), a major component of the ω-3 PUFAs family, significantly inhibited the increase of intracellular Ca2+ in cultured wild type (WT) cortical neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival compared with the vehicle-treated control. The protective effects were further confirmed in cultured neurons with high endogenous ω-3 PUFAs that were isolated from fat-1 mice, in that a higher survival rate was found in fat-1 neurons compared with wild-type neurons after OGD/R injury. Our study also found that treatment with LBP (50 mg/L) activated Trk-B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis compared with the control. Notably, both combining LBP treatment with ω-3 PUFAs administration to WT neurons and adding LBP to fat-1 neurons showed enhanced effects on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium overload and neurotrophic pathway. The results of the study suggest that ω-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.

Endogenously elevated n-3 polyunsaturated fatty acids alleviate acute ethanol-induced liver steatosis.

Effective means for the prevention of alcohol-induced liver disease, a global health problem, have yet to be developed. We evaluated whether the high endogenous levels of omega-3 polyunsaturated acids (n-3 PUFA) in fat-1 transgenic mice could protect them against acute ethanol-induced liver steatosis. We induced alcoholic liver steatosis in 9-week-old male heterozygous fat-1 mice and their wild-type (WT) male littermates through three oral gavages of 60% ethanol at 4.7 g/kg body weight. Hepatic lipid accumulation was significantly increased in both alcohol treatment groups, but by much less in the fat-1 group compared with the WT group. Fat-1 mice exhibited significantly lower levels of total hepatic/plasma TG and plasma alanine aminotransferase activity. Accordingly, hepatic expression of lipogenesis-related genes (e.g., SREBP-1c, FAS, and SCD-1) and plasma levels of inflammatory cytokines (e.g., IL-6, TNF-α, and MCP-1) were reduced in the fat-1 mice. Furthermore, decreased hepatic expression of cytochrome P450 2E1 (CYP2E1) and increased hepatic levels of PPAR-α and HO-1 were observed in the fat-1 mice, compared to the WT mice. These findings show that elevated tissue n-3 PUFA protect against acute ethanol-induced liver steatosis in fat-1 mice, possibly through the down-regulation of hepatic lipogenesis, inflammatory response, and oxidative stress.

PP.LB01.12

Objective: CHF is the inevitable outcome of all cardiovascular disease as CAD and AH. The morbidity of CHF is only 3.1 %, but at age more than 70 years, it is above 10 %. The treatment of CHF due to CAD and AH should include as first-line therapy beta-blockers or ivabradine, ACE inhibitors or ARBs with diuretics, nitrates with hydralazine (for African Americans). Amlodipine could be reserve drug in contraindications of beta-blockers or ivabradine. The additional treatment should include Aldosterone antagonists, non-dihydropyridine CCBs or Amiodarone, Digoxin as ’therapy of despair’, Aspirin, Statins, Omega-3 polyunsaturated acids. The purpose of our research was to analyze practical doctor's prescriptions for patients with CHF on base of CAD and AH. Design and method: We have studied 57 case history of patient with CHF, CAD and AH from one of therapeutic hospital in Ukraine. Doctor's prescriptions were analyzed according to modern guidelies. There are no cases of African patients. Results: Beta-blockers were prescribed to 41 patents (71.92 %), in 2 cases (3.51 %) it was non-selective one. ACE inhibitors were prescribed to 33 patients (57.89 %), ARBs to 22 (38.60 %), diuretics to 20 (35.09 %), nitrates to 6 (10.53 %), Hydralasin to no one. Dihydropyridine CCBs were in 5 cases (8.77 %), 3 of them (5.26 %) Amlodipine and 2 (3.51 %) Nifedipine. Non-dihydropyridine CCBs (Verapamil) were met in 2 cases (3.51 %). Cardiac glycoside have received 5 patients (8.77 %), 3 of them (5.26 %) digoxin, and rest sol. Corgliconi. ASA were prescribed to 40 patients (70.17 %), Statins only to 2 persons (3.51 %). Ivabradine, Amiodaron, Omega-3 polyunsaturated acids doctors have not prescribed. Patients have received 5.83 ± 1.02 drugs for treatment of CHF in average. But, there were metabolic, sedative, other drugs in case history, that were increased the number of prescriptions till 10.10 ± 2.16. Conclusions: The therapy of particular patient with CHF on base of CAD and AH should minimizing the amount of prescription drugs through the correct use of clinical pharmacological aspects of active ingredients, avoiding prescription drugs that are contraindicated in this case.

Identification of gestosis (preeclampsia) risk and evaluation of efficiency of its prevention by means of noninvasive measurement of endothelial function

Research included 64 pregnants in the I trimester with adverse anamnesis and/or clinical risk factors of preeclampsia and with revealed endothelial dysfunction by means of the device EndoPat-2000, on the basis of the reactive hyperemia index (RHI) less than 1.67, which is automatically measured by the device. Before detection of endothelial dysfunction all pregnants received basic prevention of preeclampsia with preparations of multivitamins, magnesium and progesterone. At identification of decrease in RHI to 1.3 preparation Norvesol containing omega-3 polyunsaturated fat acids (1 group, n = 32) was added. And at RHI value less than 1,3 a preparation of Angiofllux - capsular sulodexide, containing fraction of heparin 7000 Da was added. At pregnants accepting Norvesol, RHI grew in the II trimester to 1.85 ± 0.28 (р &gt; 0.05), and in the III trimester to 1.95 ± 0.19 (р &lt; 0,05 in comparison with the first research). At pregnants accepting Angioflux in the II trimester RHI increased to 1.77 ± 0.25 (р &lt; 0.05) and in III to 1.88 ± 0.20 (р ˂ 0.01 in comparison with the first research). No significant changes of indicators of system of hemostasis in dynamics were revealed in both groups. At all examined patients the delivery occurred at the full-term pregnancy. Frequency of preeclampsia development was low (21.9 and 37.5 % respectively in 1 and 2 groups), and except 1 case of middle severity in 1 group, preeclampsia didn’t exceed mild degree and didn’t influence a way of delivery and perinatal indicators. Thus, the method of functional endothelial state assessment by means of the device EndoPat-2000, allowed to specify risk degree of preeclampsia and to control efficiency of preventive therapy. At moderate violations of endothelial functional state Norvesol’s application led to correction of endothelial dysfunction and achievement of favorable outcomes of pregnancy and delivery for mother and fetus. At the cases with expressed endothelial dysfunction addition of Angioflux (sulodexide) promoted considerable improvement of endothelial function that allowed to avoid development of middle and severe preeclampsia even at pregnants with the highest risk of its development.

Impaired corticostriatal LTP and depotentiation following iPLA2 inhibition is restored following acute application of DHA.

Docosahexaenoic acid (DHA) is a 22 carbon, six cis-double bonded (22:6, w3) omega-3 polyunsaturated acid (PUFA), found highly enriched with neuronal membranes, and believed to play a critical role in synaptic plasticity and cognitive correlates of learning and memory. DHA is released from the neuronal membrane via the action of the cytostolic calcium-independent phospholipase A2 (iPLA2) enzyme. Previous studies have demonstrated that inhibition of iPLA2 by bromoenol lactone (BEL), results in inhibition of CA1 long-term potentiation (LTP), restored following acute application of DHA. In the present study, we investigated the effect of selective iPLA2 inhibition and acute application of DHA on corticostriatal synaptic plasticity. We demonstrate that acute application of 30μM DHA facilitates cotricostriatal LTP, whilst long-term depression (LTD), basal transmission, and paired-pulse facilitation (PPF) are unaffected. Conversely, selective inhibition of iPLA2, via acute application of 10μM BEL, inhibits the expression of corticostriatal LTP, with no effect on LTD. Furthermore, we show that 10μM BEL inhibition of LTP is reversed following acute application of 30μM DHA. Finally, we demonstrate that 10μM BEL inhibits depotentiation of corticostriatal LTP, which is restored following acute application of 30μM DHA. Our findings indicate that appropriate release of DHA is a critical facet of corticostriatal LTP and depotentiation, and thus provides an exciting cellular target for the positive facilitation of cognitive function observed following DHA dietary supplementation.

N-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice.

As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

Effects of supplemental long-chain omega-3 fatty acids and erythrocyte membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy adults

The long-chain omega-3 polyunsaturated (n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), may have anti-inflammatory effects. We evaluated the dose-response effect of EPA+DHA supplementation on circulating TNF-α, IL-6, and CRP and explored associations between red blood cell (RBC) membrane PUFA content and TNF-α, IL-6, and CRP. Young adults with low fish intake (n=116) received one of five doses (0, 300, 600, 900, or 1,800mg/d EPA+DHA) for 5 months. There were no significant effects of supplemental EPA+DHA on IL-6 or CRP; however, there was a marginal treatment effect for TNF-α (p<0.08). At baseline, higher quartiles of RBC DHA were associated with lower TNF-α (p=0.001); higher quartiles of arachidonic acid were associated with higher TNF-α (p=0.005). EPA+DHA supplementation had no dose-response effect on TNF-α, IL-6, or CRP in healthy young adults; however, associations between inflammatory markers and RBC PUFA warrant further investigation.

Trade-Offs Between Anti-Aging Dietary Supplementation and Exercise

In otherwise healthy adults, moderate aerobic exercise extends life span and likely health span by 2-6 years. Exercise improves blood sugar regulation, and resistance exercise increases or maintains muscle mass and is associated with improved cognitive function. On the other hand, evidence for anti-oxidant supplements increasing longevity in humans is lacking. On the contrary, transient hormetic increases in reactive oxygen species (ROS), for example, associated with exercise, are actually associated with increased mammalian health span and life span. Recent studies in humans suggest that anti-oxidants such as vitamins C, E, resveratrol, and acetyl-N-cysteine blunt the beneficial effects of exercise on glucose sensitivity and blood sugar regulation, likely through direct inhibition of ROS signaling. Alternately, other studies suggest that vitamin C has beneficial effects on exercise-associated dysfunction, inhibiting exercise-induced bronchioconstriction. These data suggest that there are tradeoffs between potential benefits and harm from anti-oxidant dietary supplementation. Specific biomolecular interactions for each antioxidant also will be important. Omega-3 (n-3) polyunsaturated fattty acids (PUFAs) have anti-inflammatory activity that is not mediated through direct ROS inhibition. Although data are limited in humans, n-3 PUFAs do not seem to blunt blood sugar regulatory benefits of aerobic exercise and actually increase anabolic activity in skeletal muscle. However, another kind of tradeoff may exist with PUFAs, at least for men. A recent large clinical trial demonstrates an association of omega-3 fatty acids blood levels with increased incidence of prostate cancer, especially aggressive prostate cancer. Together these results suggest that there are significant tradeoffs in the use of dietary supplementation for prevention and treatment of diseases associated with aging. Such tradeoffs may result from underlying intertwined homeostatic mechanisms. For most individuals, moderate exercise is of significant benefit. Careful attention to individual and family medical history and personal genomic data may prove essential to make wise dietary and supplement choices to be combined with exercise.