Abstract
Ischemia/reperfusion (I/R) injury can occur in consequence of myocardial infarction, stroke and multiple organ failure, the most prevalent cause of death in critically ill patients. I/R injury encompass impairment of endothelial dependent relaxation, increase in macromolecular permeability and leukocyte-endothelium interactions. Polyunsaturated fatty acids (n-3 PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) found in fish oil have several anti-inflammatory properties and their potential benefits against I/R injury were investigated using the hamster cheek pouch preparation before and after ischemia. Before the experiments, hamsters were treated orally with saline, olive oil, fish oil and triacylglycerol (TAG) and ethyl ester (EE) forms of EPA and DHA at different daily doses for 14 days. Fish oil restored the arteriolar diameter to pre ischemic values during reperfusion. At onset and during reperfusion, Fish oil and DHA TAG significantly reduced the number of rolling leukocytes compared to saline and olive oil treatments. Fish oil, EPA TAG and DHA TAG significantly prevented the rise on leukocyte adhesion compared to saline. Fish oil (44.83 ± 3.02 leaks/cm2), EPA TAG (31.67 ± 2.65 leaks/cm2), DHA TAG (41.14 ± 3.63 leaks/cm2), and EPA EE (30.63 ± 2.25 leaks/cm2), but not DHA EE (73.17 ± 2.82 leaks/cm2) prevented the increase in macromolecular permeability compared to saline and olive oil (134.80 ± 1.49 and 121.00 ± 4.93 leaks/cm2, respectively). On the basis of our findings, we may conclude that consumption of n-3 polyunsaturated fatty acids, especially in the triacylglycerol form, could be a promising therapy to prevent microvascular damage induced by ischemia/reperfusion and its consequent clinical sequelae.
Highlights
Ischemia/reperfusion (I/R) injury is a common consequence of several clinical conditions including myocardial infarction, stroke, organ transplantation and multiple organ failure, the most prevalent cause of death in critically ill patients [1]
reactive oxygen species (ROS) generated by endothelial cells during reperfusion seems to function like signaling molecules, inducing P-selectin translocation to endothelial surface, leukotriene B4 (LTB4) and platelet activating factor (PAF) synthesis and activation of nuclear transcription factors, such as nuclear factor-jB (NF-jB) and activator protein-1 (AP-1)
In order to investigate the role of an oral treatment with n-3 PUFA against I/R damage, we have evaluated changes on arteriolar and venular diameters, number of rolling and adherent leukocytes and microvascular permeability in post capillary venules of the hamster cheek pouch preparation before ischemia and during reperfusion
Summary
Ischemia/reperfusion (I/R) injury is a common consequence of several clinical conditions including myocardial infarction, stroke, organ transplantation and multiple organ failure, the most prevalent cause of death in critically ill patients [1]. The American Heart Association recommends the consumption of dietary supplements containing EPA and DHA ethyl esters (EE) for patients with coronary heart disease and hypertriglyceridemia [9, 10] They have potent immunomodulatory properties, limiting inflammation through several mechanisms, including: reduction of pro-inflammatory eicosanoids synthesis, increase in anti-inflammatory eicosanoids production, increase in resolvin synthesis (antiinflammatory mediators involved in inflammation resolution), decrease in leukocyte chemotaxis, inhibition of adhesion molecules expression by leukocytes and endothelial cells and reduction of NF-jB activation [11]. Clinical trials have shown that the window of opportunity to reverse deleterious effects of I/R injury is very limited since the therapeutic intervention should occur within few seconds after the onset of reperfusion [1] For this reason, there is still need of a treatment that could prevent the microvascular damage elicited by I/R [1, 12] and the consumption or ingestion of n-3 PUFA supplements could be indicated due to their anti-inflammatory properties. We have compared the anti-inflammatory efficacy between TAG and EE forms of EPA and DHA in terms of reducing microvascular permeability during I/R in the same experimental conditions
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