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

J Leukoc Biol. 2012 Jun;91(6):911-20. doi: 10.1189/jlb.0911485. Epub 2012 Apr 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Disease Models, Animal
  • Endocannabinoids
  • Ethanolamines
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Intestinal Diseases / drug therapy*
  • Intestinal Diseases / genetics
  • Intestinal Diseases / immunology
  • Intestinal Diseases / pathology
  • Intestines / immunology*
  • Intestines / pathology
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • P-Selectin / genetics
  • P-Selectin / immunology
  • PPAR alpha / genetics
  • PPAR alpha / immunology*
  • Palmitic Acids / pharmacology*
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / immunology
  • Reperfusion Injury / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / immunology


  • Amides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bax protein, mouse
  • Endocannabinoids
  • Ethanolamines
  • Interleukin-1beta
  • NF-kappa B
  • P-Selectin
  • PPAR alpha
  • Palmitic Acids
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Intercellular Adhesion Molecule-1
  • palmidrol