Disease relevance of Eicosapentaenoic acid

• Because both I(Ca,L) and sarcoplasmic reticulum Ca2+-release underlie many cardiac arrhythmias, we examined the effects of EPA on I(Ca,L) and Ca2+-sparks [1].
• Leukotriene and 5-hydroxyeicosatetraenoic acid generation was investigated in human PMN challenged with E. coli hemolysin in the absence or presence of free arachidonic acid or eicosapentaenoic acid (EPA) [2].
• AIMS/HYPOTHESIS: Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans [3].
• Mainly on the basis of the results of RCTs, the American Heart Association recommends that everyone eat oily fish twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily fish or supplements [4].
• OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults [5].

Psychiatry related information on Eicosapentaenoic acid

• Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder [6].
• In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life [7].
• Dixon plots of PEP inhibition showed oleic, linoleic, and arachidonic acids, EPA, and DHA are noncompetitive inhibitors; despite higher IC50 values of these unsaturated fatty acids than strong natural inhibitors, they may have potential use in preventing memory loss [8].
• Early developmental deficiencies in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may lower serotonin levels at critical periods of neurodevelopment and may result in a cascade of suboptimal development of neurotransmitter systems limiting regulation of the limbic system by the frontal cortex [9].
• EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry [10].

High impact information on Eicosapentaenoic acid

• In addition, cells lacking endogenous alkyl-peroxide-generating systems and thus having a low 'peroxide tone' cannot oxygenate EPA via cyclooxygenase-1 [11].
• A second major consequence of elevated EPA/AA ratios is significantly increased production of 3-series PGs, including PGE3, via cyclooxygenase-2 [11].
• Recent work has confirmed the roles of omega3 fatty acids in gene transcription and signal transduction, and has given insight into the effects of eicosapentaenoic acid (EPA) and the EPA/arachidonic acid (AA) ratio on prostanoid (PG) metabolism and function [11].
• We report the crystal structure of the PPAR delta ligand-binding domain (LBD) bound to either the FA eicosapentaenoic acid (EPA) or the synthetic fibrate GW2433 [12].
• The increased percentage of EPA and decreased percentage of AA in the phospholipids of the macrophages prepared from the fish oil-fed mice was reflected in a reduction in the amount of PGE2 and PGI2 in the medium relative to identically incubated macrophages prepared from corn oil-fed mice [13].

Chemical compound and disease context of Eicosapentaenoic acid

• Adding eicosapentaenoic acid (EPA: 5-15 micromol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias [14].
• The polyunsaturated fatty acid composition of AM phi, lung, and KE cell phospholipids can be rapidly modified by continuous short-term enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent endotoxemia [15].
• Experimental studies suggest that the risk of prostate cancer is reduced with the intake of long-chain n-3 polyunsaturated fatty acids derived from marine foods, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [16].
• In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic Acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction [17].
• Lipases from Mucor miehei (Lipozyme-IM), Pseudomonas sp. (PS-30), and Candida rugosa (AY-30) catalyzed optimum incorporation of EPA, DPA, and DHA into Laurical 35, respectively [18].

Biological context of Eicosapentaenoic acid

• During this short-term study, ingestion of both EPA and DCHA resulted in reduced platelet aggregation in response to collagen [19].
• Using a series of transformations with increasing numbers of transgenes, we demonstrate the incremental production of VLCPUFAs, achieving AA levels of up to 25% and EPA levels of up to 15% of total seed fatty acids [20].
• The IC50 of EPA was 4.8 microM [21].
• EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation [22].
• Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation [23].

Anatomical context of Eicosapentaenoic acid

• Experiments examining the influence of Promega dosage indicated that the AA/EPA ratio in neutrophil lipids decreased in a dose-dependent manner [24].
• Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids [25].
• The concentration of EPA to produce 50% inhibition of I(Ca) was 0.8 microM in neonatal rat heart cells and 2.1 microM in adult ventricular myocytes [1].
• After cardiac myocytes were treated with 5 or 10 microM EPA, the peak INa (elicited by a single-step voltage change with pulses from -80 to -30 mV) was decreased by 51% +/- 8% (P < 0.01; n = 10) and 64% +/- 5% (P < 0.001; n = 21), respectively, within 2 min [21].
• The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells [23].

Associations of Eicosapentaenoic acid with other chemical compounds

• Platelets, however, which are equipped with a lipoxygenase that can produce an abundance of hydroperoxide from AA, can form small amounts of thromboxane A3 from EPA via cyclooxygenase-1 [11].
• EPA was rapidly detected in both serum and neutrophil lipids; the arachidonic acid (AA) to EPA ratio in neutrophil phospholipids showed a maximal reduction of 49:1 to 8:1 within 1 wk of beginning supplementation [24].
• However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA [23].
• At 14 days, GLA significantly reduced the polymorphonuclear leukocyte and macrophage inflammatory infiltrate and EPA reduced the macrophage component, both with high dose; EPA also reduced keratocyte proliferation [26].
• Liquid chromatography-tandem mass spectrometry analyses of oxidized EPA demonstrated the presence of novel cyclopentenone-containing molecules termed J(3)-isoprostanes in vitro and in vivo and were shown to induce Nrf2-directed gene expression [27].

Gene context of Eicosapentaenoic acid

• We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin [3].
• AA and EPA had no effect on growth of HT-29 colon cancer cells with a low COX activity [28].
• Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA [29].
• However, stimulation of COX-2 activity by IL-1 beta resulted in a decrease in cell proliferation and an induction of cytotoxicity by AA as well as by EPA [28].
• Expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 adhesion molecules involved in SMCs migration was enhanced by AA, whereas EPA and DHA had no similar effects [30].

Analytical, diagnostic and therapeutic context of Eicosapentaenoic acid

• Metabolism and effects on platelet function of 6 g/d for 6 d of either eicosapentaenoic acid (EPA, C20:5 omega-3) or docosahexaenoic acid (DCHA, C22:6 omega-3) in volunteers were compared in a randomized crossover study [19].
• The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid a-linolenic acid is not as effective [4].
• CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats [31].
• Monocytes were incubated with or without EPA or DHA for 48 h at 37 degrees C. Following incubation, expression of major histocompatibility complex (MHC) class II molecules (HLA-DR, -DP and -DQ) and adhesion molecules [intercellular adhesion molecule-1 (ICAM-1) and leucocyte function associated antigen-1] was quantified by flow cytometry [32].
• Abbreviations: PUFA, polyunsaturated fatty acid; EPA, eicosapentanoic acid; DHA, docosahexanoic acid; and PCR, polymerase chain-reaction [33].

References