Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery

Abstract

Growing evidence highlights the importance of endogenous anti-infl ammatory mediators in appropriate modulation of infl ammatory responses and suggests that breakdowns in the metabolism of these highly bioactive molecules may underlie disease development ( 1-5 ). One key class of these metabolic regulators is the monoepoxides derived from polyunsaturated fatty acids (MEFAs), synthesized from long-chain omega-3 (n-3) and omega-6 (n-6) PUFAs by cytochrome P450 (CYP450) enzymes ( Fig. 1 ) ( 6 ). Once synthesized, MEFAs can be incorporated into membrane phospholipids or further metabolized by soluble epoxide hydrolase to their less active corresponding diols. In experimental and animal models, MEFAs have potent anti-infl ammatory and vascular protective properties, suggesting potential for development of MEFA-based therapies to target infl ammatory disorders and cardiovascular diseases ( 3, 5, 7 ). However, MEFAs have rarely been measured in humans, and important questions remain regarding their usual physiological concentrations, the interrelationship between different MEFAs derived from different classes of PUFAs, and if and by how much endogenous levels of Abstract Our objective was to assess the dynamics of monoepoxides derived from polyunsaturated fatty acids (MEFAs), and their response to n-3 PUFA supplementation, in the setting of acute tissue injury and infl ammation (cardiac surgery) in humans. Patients (479) undergoing cardiac surgery in three countries were randomized to perioperative fi sh oil (EPA + DHA; 8-10 g over 2-5 days preoperatively, then 2 g/day postoperatively) or placebo (olive oil). Plasma MEFAs derived from n-3 and n-6 PUFAs were measured 2 days postoperatively. Based on serial measures in a subset of the placebo group, levels of all MEFAs declined substantially following surgery (at postoperative day 2), with declines ranging from 37% to 63% ( P < 0.05 each). Compared with placebo at postoperative day 2, levels of EPA-and DHA-derived MEFAs were 40% and 18% higher, respectively ( P Յ 0.004). The n-3 PUFA supplementation did not signifi cantly alter the decline in n-6 PUFA-derived MEFAs. Both enrollment level and changes in plasma phospholipid EPA and DHA were associated with their respective MEFAs at postoperative day 2 ( P < 0.001). Under the acute stress of cardiac surgery, n-3 PUFA supplementation signifi cantly ameliorated the reduction in postoperative n-3 MEFAs, but not n-6 MEFAs, and the degree of increase in n-3 MEFAs related positively to the circulating level of their n-3 PUFA precursors . -Akintoye, E., J.

Fish Oil and Perioperative Bleeding

“…The within-subject change between these two time points (reflecting potential inter-individual variability in response to supplementation) was also calculated. 23 Each measure of omega-3 fatty acids was evaluated as indicator variable in quartiles in a multivariable logistic regression model that adjusted for potential confounding covariates including age, gender, race, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol, preoperative antithrombotic therapy, type of surgery, cardiopulmonary bypass use, and open vs. mini thoracotomy surgical access. 24–29 Test of linear trend across quartiles was assessed by entering the quartile variable as a single ordinal variable in the model.…”

Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers

“…Another possibility is that the AA‐derived oxylipin pool is much larger, and small changes are more difficult to detect, requiring a larger sample size. Human studies have found that ω‐3 treatment increases circulating oxylipin products of ω‐3 PUFAs, and decreases AA‐derived oxylipins, especially in the VLDL (Akintoye et al., 2016; Keenan et al., 2012; Newman et al., 2014; Schebb et al., 2014; Schuchardt et al., 2014), supporting active hepatic regulation of ω‐3 metabolism. One notable exception is subjects with low baseline levels of AA, who show an increase in both ω‐3 and ω‐6 circulating oxylipins when treated with ω‐3 PUFA (Keenan et al., 2012).…”

Effects of Omega-3 Polyunsaturated Fatty Acids, Docosahexaenoic Acid and Eicosapentaenoic Acid, on Post-Surgical Complications in Surgical Trauma Patients: Mechanisms, Nutrition, and Challenges

“…Numerous clinical trials have indeed been conducted to investigate the potential benefits of omega-3 fatty acids, specifically DHA and EPA, as nutraceuticals for improving post-surgical outcomes, particularly in the context of traumatic surgical procedures. These trials have examined various aspects of the effects of omega-3 on surgical patients, including a reduction in inflammation, enhanced immune function, pain management, improved cardiovascular health, positive effects on tissue repair, and a decrease in complications [18][19][20][21][22]. Therefore, this review paper is the first to comprehensively describe the current state of the effect of omega-3 PUFAs on post-surgical complications in trauma patients.…”