Pretreatment with wortmannin alleviates lipopolysaccharide/D-galactosamine-induced acute liver injury

Intestinal endotoxemia-induced liver injury is a common clinical disease which leads to liver failure and death. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, could be used for suppressing autophagy in vitro and in vivo. Autophagy is an evolutionarily conserved and lysosome dependent protein degradation pathway, which participates in various physiological and pathological processes. The present study aims to explore the effect of pretreatment with wortmannin on acute liver injury and the autophagy in acute liver injury. We demonstrated that wortmannin could downregulate the expression of phosphorylated extracellular regulated protein kinase and p65, decrease the production and release of hepatic inflammatory cytokines, and then reduce hepatocytes apoptosis and necrosis. More importantly, we found that autophagy was induced to increase in LPS/D-GalN-induced acute liver injury, and pretreatment with wortmannin could effectively inhibit increased autophagy in acute liver injury. In conclusion, these results indicate that wortmannin plays a protective role in LPS/D-GalN induced hepatocytotoxity maybe by inhibiting autophagy and could be acted as a target for the treatment of acute liver injury. (C) 2014 Elsevier Inc. All rights reserved.