Effects of palmitoylethanolamide on intestinal injury and inflammation caused by ischemia‐reperfusion in mice

PEA causes a substantial reduction of intestinal I/R injury in mice by reducing inflammatory mediators and apoptosis. Our primary aim in this study was to test the hypothesis that PEA, a member of the fatty acid ethanolamide family and an endogenous PPAR‐α ligand, exerts anti‐inflammatory effects on SAO shock, causing a severe form of circulatory shock and enhanced formation of ROS. SAO shock was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. In this study, we demonstrated that the administration of PEA, 5 min before reperfusion, significantly reduced all of the parameters involved during inflammation, such as proinflammatory cytokine production (TNF‐α, IL‐1β), adhesion molecules (ICAM‐1, P‐selectin) expression, NF‐κB expression, and apoptosis (Bax, Bcl‐2, TUNEL assay) activation. In addition, to study whether the protective action of PEA on SAO shock is also related to the activation of PPAR‐α, we have investigated the effect of PEA in PPAR‐α KO mice subjected to SAO shock. Our study clearly demonstrates that PEA significantly attenuated the degree of intestinal injury and inflammation caused by I/R injury. Moreover, the positive effects of PEA were at least in part dependent on the PPAR‐α pathway. The results clearly indicate that PEA exerts an anti‐inflammatory effect, also in a SAO shock model, which could imply a future use of PEA in the treatment of I/R shock.