In Vivo and in Vitro Lipid Peroxidation of Arachidonate Esters:  The Effect of Fish Oil ω-3 Lipids on Product Distribution

Abstract

The effect of lipid composition on the distribution of free radical oxidation products derived from arachidonic acid (20:4) esters has been studied in vitro and in vivo. Pro-inflammatory prostaglandin (PG) F2-like compounds, termed F2-isoprostanes (IsoPs), are produced in vivo and in vitro by the free radical-catalyzed peroxidation of arachidonic acid. Controlled free radical oxidation of mixtures of fatty acid esters in vitro showed that the formation of IsoPs from arachidonate is dramatically influenced by the presence of other fatty acid esters in the reaction mixture. Thus, three lipid mixtures containing the same arachidonate concentration but different amounts of other fatty esters (16:0; 18:1; 18:2; 20:5, and 22:6) were oxidized, and the product yields were determined by GC and LC/MS/MS analysis. The yield of F2-IsoP formed after 1 h of oxidation was 18% (based on arachidonate consumed) for mixtures containing arachidonate as the only oxidizable PUFA, but yields of these biologically active compounds dropped to 6% in polyunsaturated fatty acid (PUFA) mixtures typical of those found in tissues of fish oil-fed animals. F2-IsoP levels were also monitored in the livers of mice on diets supplemented with eicosapentaenoic acid (C20:5 omega-3; EPA), the PUFA most abundant in fish oil. While the level of arachidonic acid present in livers was not significantly different from that in control animals, levels of IsoPs in the liver were reduced in the EPA-fed mice compared to those in controls under conditions of oxidative stress (60 +/- 25% reduction, n = 5) or at baseline (48 +/- 14% reduction, n = 5). These results suggest that dietary omega-3 PUFAs may influence the formation of bio-active peroxidation products derived from omega-6 PUFAs by channeling the free radical pathway away from the F2-IsoPs.

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

“…Of note, SIRT1 can also interfere with NF-κB signalling. AC, acetyl group; P, phosphate reflecting possibly the ability of EPA-and DHA-derived peroxyl radicals to favour the formation of 'less proinflammatory' peroxidation products derived form AA [38].…”

Quantitative analysis of phospholipids containing arachidonate and docosahexaenoate chains in microdissected regions of mouse brain

“…Phosphatidylserines are also enriched in DHA chains, because the enzymes that synthesize the PS headgroup prefer substrates containing DHA ( 36 ). The presence of DHA chains alters the distribution of AA-derived oxidation products ( 61 ). The signifi cance of such fi ndings in vivo is unknown, but they relate in an interesting way to in Given measured values of r, AA C , and DHA C for any given headgroup, s may be calculated from Table 4 .…”

Formation of Highly Reactive Cyclopentenone Isoprostane Compounds (A3/J3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

“…In addition to identifying enzymatically generated oxygenated derivatives of EPA, there has been significant interest in studying the beneficial effects of non-enzymatically derived EPA peroxidation products (8,16,48). Sethi and co-workers (4 -6) reported Cu 2ϩ -oxidized EPA, but not native EPA, potently inhibits human neutrophil and monocyte adhesion to endothelial cells, a process linked to atherosclerosis.…”