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Arachidonic acid

About: Arachidonic acid is a research topic. Over the lifetime, 19417 publications have been published within this topic receiving 775369 citations. The topic is also known as: all-cis-5,8,11,14-eicosatetraenoic acid & cis-Delta(5,8,11,14)-eicosatetraenoic acid.


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Journal ArticleDOI
TL;DR: At sufficiently high intakes, long-chain n-3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules, and are potentially potent antiinflammatory agents.
Abstract: Inflammation is part of the normal host response to infection and injury. However, excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases and is characterized by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids (prostaglandins, thromboxanes, leukotrienes, and other oxidized derivatives), other inflammatory agents (e.g., reactive oxygen species), and adhesion molecules. At sufficiently high intakes, long-chain n-3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules. Long-chain n-3 PUFAs act both directly (e.g., by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly (e.g., by altering the expression of inflammatory genes through effects on transcription factor activation). Long-chain n-3 PUFAs also give rise to a family of antiinflammatory mediators termed resolvins. Thus, n-3 PUFAs are potentially potent antiinflammatory agents. As such, they may be of therapeutic use in a variety of acute and chronic inflammatory settings. Evidence of their clinical efficacy is reasonably strong in some settings (e.g., in rheumatoid arthritis) but is weak in others (e.g., in inflammatory bowel diseases and asthma). More, better designed, and larger trials are required to assess the therapeutic potential of long-chain n-3 PUFAs in inflammatory diseases. The precursor n-3 PUFA alpha-linolenic acid does not appear to exert antiinflammatory effects at achievable intakes.

2,293 citations

Journal ArticleDOI
TL;DR: It is concluded that the synthesis ofIL-1 beta, IL-1 alpha, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n-3 fatty acids.
Abstract: We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n-3 fatty acids. Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1 beta and IL-1 alpha) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1 beta was suppressed from 7.4 +/- 0.9 ng per milliliter at base line to 4.2 +/- 0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9 +/- 0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1 alpha and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1 beta, IL-1 alpha, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells. We conclude that the synthesis of IL-1 beta, IL-1 alpha, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n-3 fatty acids. The reported antiinflammatory effect of these n-3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor.

1,889 citations

Journal ArticleDOI
TL;DR: Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases.
Abstract: Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil— eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are more biologically potent than -linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn’s disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebocontrolled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs. Key teaching points:  In Western diets, omega-6 fatty acids are the predominant polyunsaturated fats. The omega-6 and omega-3 fatty acids are metabolically distinct and have opposing physiologic functions.  Eicosapentaenoic acid (EPA) is released to compete with arachidonic acid (AA) for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.  Animal and human studies support the hypothesis that omega-3 PUFA suppress cell mediated immune responses.  In experimental animals and humans, serum PUFA levels predict the response of proinflammatory cytokines to psychologic stress. Imbalance in the omega-6/omega-3 PUFA ratio in major depression may be related to the increased production of proinflammatory cytokines and eicosanoids in that illness.  The increased omega-6/omega-3 ratio in Western diets most likely contributes to an increased incidence of cardiovascular disease and inflammatory disorders.  Patients with autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and asthma, usually respond to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by decreasing the elevated levels of cytokines.

1,798 citations

Journal ArticleDOI
14 Jun 1991-Cell
TL;DR: The cloning and expression of a cDNA encoding a high molecular weight cytosolic phospholipase A2 (cPLA2) that has no detectable sequence homology with the secreted forms of PLA2 is reported and it is demonstrated that cPLA2 selectively cleaves arachidonic acid from natural membrane vesicles and translocates to membrane vESicles in response to physiologically relevant changes in free calcium.
Abstract: We report the cloning and expression of a cDNA encoding a high molecular weight (85.2 kd) cytosolic phospholipase A 2 (cPLA 2 ) that has no detectable sequence homology with the secreted forms of PLA 2 . We show that cPLA 2 selectively cleaves arachidonic acid from natural membrane vesicles and demonstrate that cPLA 2 translocates to membrane vesicles in response to physiologically relevant changes in free calcium. Moreover, we demonstrate that an amino-terminal 140 amino acid fragment of cPLA 2 translocates to natural membrane vesicles in a Ca 2+ -dependent fashion. Interestingly, we note that this 140 amino acid domain of cPLA 2 contains a 45 amino acid region with homology to PKC, p65, GAP, and PLC. We suggest that this homology delineates a Ca 2+ -dependent phospholipid-binding motif, providing a mechanism for the second messenger Ca 2+ to translocate and activate cytosolic proteins.

1,652 citations

Journal ArticleDOI
TL;DR: Unlike arachidonic acid, eicosapentaenoic acid (C20:5omega-3, E.P.A.) does not induce platelet aggregation in human platelet-rich plasma (P.R.X.A.P.), probably because of the formation of thromboxane A3 (T.G.I3) which does not have platelet aggregating properties.
Abstract: Unlike arachidonic acid (eicosatetraenoic acid, C20:4omega-6, AA), eicosapentaenoic acid (C20:5omega-3, EPA) does not induce platelet aggregation in human platelet-rich plasma (PRP), probably because of the formation of thromboxane A3 (TXA3) which does not have platelet aggregating properties Moreover, EPA, like AA, can be utilised by the vessel wall to make an anti-aggregating substance, probably a delta17-prostacyclin (PGI3) This finding suggests that, in vivo, high levels of EPA and low levels of AA could lead to an antithrombotic state in which an active PGI3 and a non-active TXA3 are formed Eskimos have high levels of EPA and low levels of AA and they also have a low incidence of myocardial infarction and a tendency to bleed It is possible that dietary enrichment with EPA will protect against thrombosis

1,632 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20251
2023280
2022444
2021231
2020226
2019245