Is pyruvate an endogenous anti-inflammatory molecule?

Pyruvic acid is an effective scavenger of reactive oxygen species. Ethyl pyruvate has demonstrated anti-inflammatory actions and improved hyperpermeability and bacterial translocation due to endotoxemia and is of benefit in animal models of sepsis and septic shock. Ethyl pyruvate specifically inhibits tumor necrosis factor-a production and decreases circulating levels of high-mobility group box-1 and nuclear factor-kappa B signaling pathways by specifically targeting its p65 subunit in animals with established endotoxemia or sepsis and in macrophage cultures. Ethyl pyruvate also decreases cyclo-oxygenase-2, inducible nitric oxide synthase, and interleukin-6 mRNA expression in the liver, ileal mucosa, and colonic mucosa in animal models with hemorrhagic shock. Similar beneficial actions have been seen in endotoxemia. These and other studies suggest that ethyl pyruvate could be of significant benefit in the treatment of patients who are critically ill and have sepsis/septic shock. (c) 2006 Elsevier Inc. All rights reserved.