Showing papers on "Docosahexaenoic acid published in 1986"

Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys

Abstract: Docosahexaenoic acid [22:6 omega 3; 22:6-(4,7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other omega 3 fatty acids, chiefly alpha-linolenic acid (18:3 omega 3). We tested the effect of dietary omega 3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurified diets very low in 18:3 omega 3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3 omega 3. In near-term fetuses and newborn infants of the deficient group, the 22:6 omega 3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6 omega 3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6 omega 3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain omega 6 fatty acids, particularly 22:5 omega 6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary omega 3 fatty acids are retina and brain.

Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function

Abstract: The effects of dietary fish-oil fatty acids on the function of the 5-lipoxygenase pathway of peripheral-blood polymorphonuclear leukocytes and monocytes were determined in seven normal subjects who supplemented their usual diet for six weeks with daily doses of triglycerides containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid. The diet increased the eicosapentaenoic acid content in neutrophils and monocytes more than sevenfold, without changing the quantities of arachidonic acid and docosahexaenoic acid. When the neutrophils were activated, the release of [3H]arachidonic acid and its labeled metabolites was reduced by a mean of 37 per cent, and the maximum generation of three products of the 5-lipoxygenase pathway was reduced by more than 48 per cent. The ionophore-induced release of [3H]arachidonic acid and its labeled metabolites from monocytes in monolayers was reduced by a mean of 39 per cent, and the generation of leukotriene B4 by 58 per cent. The adherence of neutrophils to bovine endothelial-cell monolayers pretreated with leukotriene B4 was inhibited completely, and their average chemotactic response to leukotriene B4 was inhibited by 70 per cent, as compared with values determined before the diet was begun and six weeks after its discontinuation. We conclude that diets enriched with fish-oil-derived fatty acids may have antiinflammatory effects by inhibiting the 5-lipoxygenase pathway in neutrophils and monocytes and inhibiting the leukotriene B4-mediated functions of neutrophils.

Effects of Dietary Supplementation of Fish Oil on Neutrophil and Epidermal Fatty Acids: Modulation of Clinical Course of Psoriatic Subjects

Abstract: † Findings from an eight-week fish oil-supplemented diet given to 13 psoriatic patients demonstrated that eicosapentaenoic acid (20:5,n3 [EPA]) and docosahexaenoic acid (22:6,n3 [DCHA]) are rapidly incorporated into the sera, neutrophils, and epidermis of participating patients, and that the incorporation of EPA and DCHA into epidermal lipids increased with weeks of supplementation with minimal alteration of arachidonic acid (AA) in the epidermal lipids. Global clinical evaluation showed that eight patients demonstrated mild to moderate improvement in their psoriatic lesions. Improved clinical response correlated with high EPA/DCHA ratios attained in epidermal tissue specimens. These findings underscore the need for further investigations into the role of dietary n3 fatty acids, particularly the possibility of pentaenoic acid as a potential protective agent and/or therapeutic adjunct for the clinical management of psoriasis. ( Arch Dermatol 1986;122:1277-1282)

Effect of dietary supplementation with fish oil on systolic blood pressure in mild essential hypertension.

Abstract: pressures related to situation and the influence of other drug users. In the outpatient group the most risky times appeared to be at the beginning and end of the withdrawal schedule. Six subjects (21% ofthis group) failed in the first 14 days of the eight week programme, and 9 (31%) failed in the last week. Ofthe six inpatients who failed, two did so on the first day and the four others in the last six days. The outpatient sample was more likely to remain in contact with the hospital's drug dependence services (x2=9 19, p

Recovery of altered fatty acid composition induced by a diet devoid of n-3 fatty acids in myelin, synaptosomes, mitochondria, and microsomes of developing rat brain.

Abstract: Rats were fed a semisynthetic diet containing either sunflower oil or soya oil. Half the litter fed with sunflower oil diet was changed to a soya oil diet when the pups were 15 days old (during active myelination). Fatty acid analysis was then performed on subcellular fractions of the animals fed (a) soya oil, (b) sunflower oil, and (c) soya oil replacing sunflower oil from the 15th day, to determine the speed of the recovery. All material from animals fed sunflower oil showed an important reduction in docosahexaenoic acid (22:6 n-3), compensated by an increase in docosapentaenoic acid (22:5 n-6), whereas arachidonic acid (20:4 n-6) was not affected. In all fractions examined, when sunflower oil was replaced by soya oil in 15-day-old pups the recovery started from the very first day but lasted more than 2 months (this recovery was determined by the increase of 22:6 n-3 up to the normal value and decrease of the 22:5 n-6). In addition a delay was found for myelin recovery, starting only from the 25th day.

Fish oil modifies lipids and reduces platelet aggregability in haemodialysis patients.

Abstract: Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Polyunsaturated fatty acids and vitamin E in rat rod outer segments during light damage.

Abstract: Previous evidence suggests that lipid peroxidation may initiate photoreceptor damage induced by constant light exposure. In order to investigate the role of the antioxidant vitamin E in light damage, Long-Evans (pigmented) rats were atropinized and exposed to constant fluorescent light (Vita-Lite) of 10-20 foot candles for intervals up to 5 days. Following light exposure, retinal rod outer segments (ROS) were prepared and their lipids extracted. Retinas processed in parallel for morphological examination showed progressive ROS deterioration and selective loss of photoreceptor cells at 3 and 5 days of constant light. Similar to previous observations in undilated albino rats, constant illumination resulted in the specific loss of docosahexaenoic acid (22:6 omega 3) in the ROS. A novel finding in this study was an increase in the content of vitamin E relative to lipid phosphorus, stearic acid, and docosahexaenoic acid in the ROS of constant light-exposed animals.

In vitro incorporation and metabolism of icosapentaenoic and docosahexaenoic acids in human platelets--effect on aggregation.

Abstract: Washed human platelets were pre-loaded with icosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or EPA + DHA and tested for their aggregation response in comparison with control platelets. In fatty acid-rich platelets, an inhibition of the aggregation could be observed when induced by thrombin, collagen or U-46619. The strongest inhibition was observed with DHA-rich platelets and it was reduced when DHA was incorporated in the presence of EPA. Study of fatty acid distribution in cell lipids after loading showed that around 90% of EPA or DHA taken up was acylated into phospholipids and a very small amount (less than 2%) remained in their free and hydroxylated forms. DHA was more efficiently acylated into phosphatidylethanolamine (PE) than into phosphatidylinositol (PI) in contrast to what observed with EPA, and both acids were preferentially incorporated into phosphatidylcholine (PC). EPA inhibited total incorporation of DHA and increased its relative acylation into PE at the expense of PC. In contrast, DHA did not affect the acylation of EPA. Upon stimulation with thrombin, EPA was liberated from phospholipids and oxygenated (as judged by the formation of its monohydroxy derivative) whereas DHA was much less metabolized, although consistently transferred into PE. It is concluded that EPA and DHA might affect platelet aggregation via different mechanisms when pre-loaded in phospholipids. Whereas EPA is known to alter thromboxane A2 metabolism from endogenous arachidonic acid, by competing with it, DHA might act directly at the membrane level for inhibiting aggregation.

Fatty acid composition of plasma lipids in Nigerian children with protein-energy malnutrition

Abstract: The fatty acid (FA) composition of the main plasma lipids was analysed in eight well-nourished, generally healthy Nigerian children aged 14.1±7.2 months and in 17 malnourished children (8 marasmus, 9 kwashiorkor) aged 14.6±3.8 months within the first 2 days of admission at the Dept. of Child Health, University of Benin. In comparison to the control group, the malnourished children showed a marked decrease of polyunsaturated FA with low linoleic acid, mainly in sterolesters (STE), and severely reduced linoleic acid metabolites, including arachidonic acid, in all lipid fractions. ω-3-FA were not altered except for a reduction of docosapentaenoic and docosahexaenoic acids in phospholipids. Clearly increased values were found for saturated FA in STE and for the non-essential monoenoic FA in all lipid classes. This pattern indicates the presence of essential fatty acid deficiency in the malnourished children. There was no significant difference between marasmus and kwashiorkor. Eight malnourished children were followed up in the early phase of recovery during hospital treatment 14.0±3.1 days after obtaining the first sample. Linoleic acid had increased again in STE, but its metabolites were as low or even lower than before. An impaired activity of delta-6-desaturase, the rate limiting enzyme of linoleic acid metabolism, in suggested by elevated substrate-product-ratios of this enzyme in untreated children with protein energy malnutrition and in the early phase of recovery, which may be due to low insulin levels, protein and zinc deficiency. The trientetraen-ratio (20∶3ω9/20∶4ω6) thus is not a reliable indicator of essential FA status in protein-energy malnutrition.

Arachidonic acid metabolism by the 5-lipoxygenase pathway, and the effects of alternative dietary fatty acids.

Abstract: Publisher Summary This chapter reviews the recent studies of the effects of EPA and DCHA on leukotriene generation and function. The beneficial effects of fish oils on ischemic heart disease have been attributed to the effects of eicosapentaenoic acid (EPA) on plasma cholesterol and triglyceride levels and on the attenuation of the cyclooxygenase pathway and certain products to modify platelet and endothelial cell interactions in a favorable direction. Supplementation of the diet with 40 ml/day of cod liver oil provides about 4–5 g of EPA and about 5–6 g of docosahexaenoic acid (DCHA) daily; increases the bleeding time and decreases the platelet count; suppresses the platelet aggregation response to ADP and collagen stimulation; and reduces the associated formation of immunoreactive thromboxane B, which is a metabolic product of thromboxane A and serves to uantitate the active product. To appreciate the possible effects of alternative fatty acids on the function and products of the 5-lipoxygenase pathway, it is appropriate to consider the steps in biosynthesis and metabolism of the leukotrienes, the nature of subclass-specific receptors, and the pharmacologic and likely physiologic actions of the leukotrienes. Clinical investigation has focused exclusively on the effects of N-3 fatty acids in the modulation of the metabolism of arachidonic acid by the cyclooxygenase pathway. Because arachidonic acid released from membrane phospholipids can also be metabolized by lipoxygenase pathways of which the 5-lipoxygenase pathway leads to the generation of the proinflammatory leukotrienes.

Enhancement of plasma levels of biologically active leukotriene B compounds during anaphylaxis in guinea pigs pretreated by indomethacin or by a fish oil-enriched diet.

Abstract: The changes in arterial plasma concentrations of immunoreactive leukotriene B (LTB) were compared after antigen challenge of two groups of sensitized, mepyramine-treated, and mechanically ventilated guinea pigs, one fed a diet enriched with fish oil and the other a control diet enriched with beef tallow. The lung tissue of animals fed a fish oil-enriched diet (FFD) for 9 to 10 wk incorporated eicosapentaenoic acid (EPA) and docosahexaenoic acid to constitute 8 to 9% of total fatty acid content, whereas these alternative fatty acids constituted less than 1% of the total fatty acid content of the lung tissue of animals on a beef tallow-supplemented diet (BFD). The maximum increase after antigen challenge in immunoreactive LTB4 from 0.16 +/- 0.04 ng/ml to 0.84 +/- 0.25 ng/ml in BFD animals and from 0.47 +/- 0.11 to 5.1 +/- 1.4 ng/ml immunoreactive LTB (LTB4 and LTB5) in FFD animals was significant (p less than 0.02) for each. Furthermore, the increase in total immunoreactive LTB in mepyramine-treated FFD animals was significantly greater than the increase in LTB4 in mepyramine-treated BFD guinea pigs at 2 to 8 min after antigen challenge (p less than 0.05). Resolution of arterial plasma immunoreactive LTB from pooled samples by reverse-phase high-performance liquid chromatography demonstrated that the sum of LTB4 and LTB5 in FFD animals exceeded that of LTB4 in BFD animals and that the quantity of LTB4 in the FFD animals was at least as great as that in the BFD animals during anaphylaxis. The products eluting at the retention times of LTB4 and LTB5 exhibited the chemotactic activity of their respective synthetic standards. The combination of indomethacin and mepyramine markedly augmented the antigen-induced increase in arterial plasma immunoreactive LTB4 concentrations in BFD animals, but had no effect on immunoreactive LTB levels in FFD animals. Limited in vivo measurements showing a lesser increase of plasma immunoreactive thromboxane B2 in the FFD relative to the BFD animals during anaphylaxis and ex vivo measurements showing a decreased LTB4-stimulated (cyclooxygenase product-dependent) contractile response of pulmonary parenchymal strips from the FFD relative to the BFD animals provide evidence for blockade in the cyclooxygenase pathway in the FFD animals. The measurements of arterial plasma LTB indicate that indomethacin treatment alone, which inhibits cyclooxygenase activity, and FFD treatment each augment the metabolism of arachidonic acid by the 5-lipoxygenase pathway in animals pretreated with mepyramine.(ABSTRACT TRUNCATED AT 400 WORDS)

Fatty Acid Composition Transport and Metabolism in Doxorubicin-sensitive and -resistant Rat Glioblastoma Cells

Abstract: We have studied the lipid composition and the acyl group composition, transport, and metabolism of doxorubicin-sensitive and -resistant rat glioblastoma cells in monolayer cultures (C6 clone). No difference in lipid composition was evidenced; the acyl group composition was, in contrast, highly modified in resistant cells, and these modifications appeared progressively during the acquisition of the resistance. Resistant cells were characterized by a decrease of n-9 eicosatrienoic acid and by a 2-3-fold increase of the proportions of the polyunsaturated fatty acids of the n-6 and n-3 families, especially arachidonic acid and n-3 docosahexaenoic acid. These differences were probably due to a 2-fold increase of the uptake of fatty acids by resistant cells as compared to sensitive cells, this increase allowing the suppression of an essential fatty acid deficiency. Only small changes in the transformations of 16 and 18-carbon atoms' fatty acids to higher analogues were evidenced. A small reduction of the desaturation of stearic acid to oleic acid and of linoleic acid to arachidonic acid was the main characteristic of resistant cells; these differences can be explained as a consequence of the suppression of the essential fatty acid deficiency.

Manipulation of rat brain fatty acid composition alters volatile anesthetic potency.

Abstract: The molecular mechanism of volatile anesthetic action remains unknown. Attempts to elucidate this mechanism have been complicated by the absence of models in which changes in neuronal cellular properties can be correlated with changes in whole animal anesthetic effect. In this study we describe a model where diet-induced alterations in rat brain fatty acid composition are correlated with alterations in volatile anesthetic potency. Rats maintained on a fat-free diet showed significant depletion of arachidonic acid (20:4 omega 6; 5,8,11,14-eicosatetraenoic acid) and docosahexaenoic acid (22:6 omega 3; 4,7,10,13,16,19,-docosahexaenoic acid) in brain, and a corresponding increase in Mead acid (20: 3 omega 9; 5,8,11-eicosatrienoic acid). These fat-deprived rats were significantly more sensitive to all volatile anesthetics tested than were age-controlled rats on a normal diet. Parenteral supplementation of the fat-deprived animals with linolenic acid (18: 3 omega 3, 9,12,15-octadecatrienoic acid) completely reconstituted the docosahexaenoic acid content of brain without affecting anesthetic sensitivity. In contrast, supplementation of the fat-deprived rats with linoleic acid (18: omega 6; 9,12-octadecadienoic acid) caused a dramatic decrease in anesthetic sensitivity, but only a small change in whole brain arachidonate content. Further analysis revealed that linoleate supplementation of fat-deprived animals resulted in a preferential normalization of the arachidonate content of brain phosphatidylinositol as compared with other brain phosphoglycerides. These results demonstrate for the first time a correlation between changes in membrane composition and anesthetic effect, and indicate that the precise fatty acid composition (perhaps in specific phospholipids) of brain is important in the mechanism of volatile anesthetic action.

Refined fish oil concentrate and the production process for same

Abstract: Refining of fish waste product so that a concentrate of .omega.3-fatty acid alkyl ester is formed with 20-30% eicosa-pentaenoic acid alkyl ester and 35-50% docosahexaenoic acid alkyl ester (both by weight) free from cholesterol. The .omega.3-concentrate is produced through urea precipitation of the non- .omega.3-fatty acid esters so that the filtrate from the pre-cipitation may be extracted by means of hexane for the trans-mission of the .omega.3-fatty acid esters and the cholesterol to the hexane extract, Hexane is thereafter removed. The remaining concentrate of the fatty acid esters with the chol-esterol is cooled to a temperature of not lower than -50°C, whereby the cholesterol is crystallized. The remainder is a .omega.3-concentrate with the composition mentioned above.

Lipoxygenase‐Catalyzed Oxidation of N‐6 and N‐3 Polyunsaturated Fatty Acids: Relevance to and Activity in Fish Tissue

Abstract: Lipid peroxidation is an important process responsible for the flavor deterioration of many plant and animal foods. In order to understand possible mechanisms of initiation, a soybean lipoxygenase-polyunsaturated fatty acid model system was studied. The rate of enzyme-initiated oxidation was monitored by both oxygen consumption and diene conjugation. The hydroperoxides from an n-6 fatty acid, i.e. arachidonic, and n-3 fatty acids, i.e. linolenic, eicosapentaenoic, and docosahexaenoic acids were reduced and analyzed by reverse-phase high pressure liquid chromatography and gas chromatography/mass spectrometry. The lipoxygenase specifically catalyzed oxygenation at the n-6 carbon of both n-3 and n-6 fatty acids. Lipoxygenase activity was demonstrated in skin homogenate from rainbow trout and its role in off-flavor development is discussed.

Acylation of docosahexaenoic acid into phospholipids by intact human neutrophils

Abstract: Docosahexaenoic acid was not only acylated into phospholipids but also into triacylglycerols by intact human neutrophils. The distribution of radiolabeled docosahexaenoic acid among individual phospholipids was dependent on the incubation time. [1-14C]Docosahexaenoic acid at all concentrations (1 to 8 microM) was acylated mainly into phosphatidic acid after 1-2 min incubation, and the radioactivity of phosphatidic acid started to decline after a longer period of incubation, suggesting the participation of docosahexaenoyl-phosphatidic acid in the synthesis of other glycerolipids. It was acylated primarily into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) after a 2-hr incubation. The labeled phosphatidic acid may be rapidly deacylated and the 22:6(n-3) moiety is then reacylated into other lysophospholipids. The low levels of [14C]22:6(n-3) in 1,2-diacylglycerol suggest that the deacylation-reacylation cycle may be a major pathway in the formation of [14C]22:6(n-3)-PC and -PE in intact neutrophils. This n-3 fatty acid was a relatively poor substrate for acylation into phosphatidylinositol as compared to arachidonic acid and eicosapentaenoic acid. However, the patterns of distribution of all three polyunsaturated fatty acids among the diacyl- and ether-linked class compositions of PC and PE were similar. These data suggest the potential of increasing the content of docosahexaenoic acid of membrane lipids in neutrophils by dietary supplement of this fatty acid.