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Project Title:
Ethyl Pyruvate: A Novel Treatment for Sepsis
Funding Agency:
National Institute of General Medical Science
Total Project Period:
Jul 01, 2003 - Jun 28, 2008
Principal Investigator:
Mitchell Fink, MD
Co-Investigator(s):
Russell Delude, PhD
Project Summary:
Ethyl pyruvate (EP) is the ester formed from pyruvic acid and ethanol in preliminary studies, we have documented that EP ameliorates intestinal and hepatic injury or improves survivial when it is used as a therapeutic agent to treat rodents subjected to mesenteric ischemia and reperfusion (I/R), hemorrhagic shock (HS), endotoxemia, or polymicrobial bacterial sepsis. In addition, we have demonstrated that EP is an effective scavenger of reactive oxygen species (ROS), and we have shown that this compound is also an anti-inflammatory agent that inhibits activation of the pro-inflammatory signaling factors, NF- and p38 mitogen-activated protein kinase (MAPK). EP also inhibits release of a novel cytokine, high mobility group box 1 (HMGB1). Prompted by these exciting observations, we propose to carry out a series of experiments that are designed to better elucidate the mechanism(s) responsible for the anti-inflammatory and therapeutic effects of EP.
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