title: Effects of palmitoylethanolamide on intestinal injury and inflammation caused by ischemia-reperfusion in mice.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Agata
authors.initials: A
authors.lastname: Torre
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cappellani
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Francesca
authors.initials: F
authors.lastname: Trischitta
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004195:Disease Models, Animal; D063388:Endocannabinoids; D004983:Ethanolamines; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D019007:P-Selectin / Q000235:genetics / Q000276:immunology; D047493:PPAR alpha / Q000235:genetics / Q000276:immunology*; D010169:Palmitic Acids / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000276:immunology
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; C494827:Bax protein, mouse; D063388:Endocannabinoids; D004983:Ethanolamines; D053583:Interleukin-1beta; D016328:NF-kappa B; D019007:P-Selectin; D047493:PPAR alpha; D010169:Palmitic Acids; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1; C005958:palmidrol