Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock

Am J Physiol Gastrointest Liver Physiol. 2002 Jul;283(1):G212-21. doi: 10.1152/ajpgi.00022.2002.


Administration of pyruvate, an effective scavenger of reactive oxygen species, has been shown to be salutary in numerous models of redox-mediated tissue or organ injury. Pyruvate, however, is unstable in solution and, hence, is not attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which is thought to be more stable than the parent compound, was formulated in a calcium-containing balanced salt solution [Ringer ethyl pyruvate solution (REPS)] and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R). Resuscitation with REPS instead of Ringer lactate solution (RLS) significantly improved survival at 24 h and abrogated bacterial translocation to mesenteric lymph nodes and the development of increased ileal mucosal permeability to FITC-labeled dextran (4,000 Da) at 4 h. Mice treated with REPS instead of RLS also had lower circulating levels of alanine aminotransferase at 4 h. Treatment with REPS instead of RLS decreased activation of nuclear factor-kappaB in liver and colonic mucosa after HS/R and also decreased the expression of inducible nitric oxide synthase, tumor necrosis factor, cyclooxygenase-2, and interleukin-6 mRNA in liver, ileal mucosa, and/or colonic mucosa. These data support the view that resuscitation with REPS modulates the inflammatory response and decreases hepatocellular and gut mucosal injury in mice subjected to HS/R.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Down-Regulation
  • Gene Expression / drug effects*
  • Inflammation / genetics*
  • Intestinal Mucosa / physiopathology
  • Isotonic Solutions / pharmacology*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / physiology
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Resuscitation
  • Ringer's Lactate
  • Shock, Hemorrhagic / genetics*
  • Shock, Hemorrhagic / pathology
  • Shock, Hemorrhagic / physiopathology
  • Shock, Hemorrhagic / therapy
  • Survival Analysis


  • Isotonic Solutions
  • NF-kappa B
  • Ringer's Lactate
  • Ringer's ethyl pyruvate
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse