“…Therefore, we proposed that HMGB1 as an important inflammatory mediator of endotoxemia should also play a significant role in the pathogenesis of liver failure [20] . Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has been shown to improve survival and ameliorate organ dysfunction in a variety of animal models of critical illness, including acute endotoxemia [21] , polymicrobial bacterial sepsis [22] , postsurgical ileus [23] , burn injury [24] , acute pancreatitis [25] , organ ischemia and reperfusion injury [26,27] , and hemorrhagic shock [28] . As an effective anti-inflammatory agent, EP inhibits the activation of key inflammatory signaling pathways [29,30] , and down-regulates the secretion of multiple inflammatory proteins, including IL-6, TNF-α and HMGB1 [31][32][33] .…”