| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Critical Care Medicine, 2 Surgery, and 4 Pathology, and 3 Center for Biologic Imaging, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261
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-
B 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.
translocation; bacterial; permeability; mucosal; tumor necrosis factor; cyclooxygenase-2; inducible nitric oxide synthase
This article has been cited by other articles:
|
|
 |
|
  A. Leelahavanichkul, H. Yasuda, K. Doi, X. Hu, H. Zhou, P. S. T. Yuen, and R. A. Star Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1825 - F1835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lee, W. Kwon, Y. Jo, G. Suh, and Y. Youn Protective effects of ethyl pyruvate treatment on paraquat-intoxicated rats Human and Experimental Toxicology, January 1, 2008; 27(1): 49 - 54. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Su, Z. Wang, Y. Cai, M. Remmelink, and J.-L. Vincent Beneficial Effects of Ethyl Pyruvate in Septic Shock From Peritonitis Arch Surg, February 1, 2007; 142(2): 166 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Raman, P. L. Sappington, R. Yang, R. M. Levy, J. M. Prince, S. Liu, S. K. Watkins, A. M. Schmidt, T. R. Billiar, and M. P. Fink The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G556 - G565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Luyer, J. W. M. Greve, M. Hadfoune, J. A. Jacobs, C. H. Dejong, and W. A. Buurman Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve J. Exp. Med., October 17, 2005; 202(8): 1023 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Han, J. A. Englert, R. Yang, R. L. Delude, and M. P. Fink Ethyl Pyruvate Inhibits Nuclear Factor-{kappa}B-Dependent Signaling by Directly Targeting p65 J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Woo, M. D. Taylor, J. E. Cohen, V. Jayasankar, L. T. Bish, J. Burdick, T. J. Pirolli, M. F. Berry, V. Hsu, and T. Grand Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia J. Thorac. Cardiovasc. Surg., May 1, 2004; 127(5): 1262 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Han, M. P. Fink, T. Uchiyama, R. Yang, and R. L. Delude Increased iNOS activity is essential for pulmonary epithelial tight junction dysfunction in endotoxemic mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L259 - L267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Song, J. A. Kellum, H. Kaldas, and M. P. Fink Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 307 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yang, X. Han, T. Uchiyama, S. K. Watkins, A. Yaguchi, R. L. Delude, and M. P. Fink IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G621 - G629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Sappington, X. Han, R. Yang, R. L. Delude, and M. P. Fink Ethyl Pyruvate Ameliorates Intestinal Epithelial Barrier Dysfunction in Endotoxemic Mice and Immunostimulated Caco-2 Enterocytic Monolayers J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 464 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yang, D. J. Gallo, J. J. Baust, S. K. Watkins, R. L. Delude, and M. P. Fink Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1263 - R1274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ulloa, M. Ochani, H. Yang, M. Tanovic, D. Halperin, R. Yang, C. J. Czura, M. P. Fink, and K. J. Tracey Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation PNAS, September 17, 2002; 99(19): 12351 - 12356. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
