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

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-alpha 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 pro-inflammatory cytokine production (TNF-alpha, IL-1 beta), adhesion molecules (ICAM-1, P-selectin) expression, NF-kappa B 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-alpha, we have investigated the effect of PEA in PPAR-alpha 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-alpha 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. J. Leukoc. Biol. 91: 911-920; 2012.