Oleoylethanolamide Alleviates Hepatic Ischemia-Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress-Associated Apoptosis.

Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPAR α involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPAR α ) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPAR α , thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPAR α activation could be an effective therapy against hepatic ischemia/reperfusion injury.