Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis.
OBJECTIVE
Ethyl pyruvate has been shown to be an effective anti-inflammatory agent in a variety of in vitro and in vivo model systems. Herein, we used a murine model of acute pancreatitis to compare the effects of treatment with either Ringer's lactate solution or ethyl pyruvate solution on several physiologic and biochemical variables related to disease severity.


METHODS
Experimental animal study.


METHODS
University laboratory.


METHODS
C57Bl/6 mice.


METHODS
Pancreatitis was induced by feeding the animals a choline-deficient diet supplemented with 0.5% ethionine for 24 hrs and then challenging the animals with seven hourly 50 microg/kg intraperitoneal injections of cerulein and a single intraperitoneal injection of Escherichia coli lipopolysaccharide (4 mg/kg).


RESULTS
When mice were treated with ethyl pyruvate (40 mg/kg intraperitoneally every 6 hrs for 48 hrs) instead of Ringer's lactate solution starting 2 hrs after the injection of lipopolysaccharide, long-term survival was improved from one of ten to six of ten (p =.057). When mice were treated with a 40 mg/kg dose of ethyl pyruvate just before the first dose of cerulein and then injected with a second 40 mg/kg dose 6 hrs later, serum concentrations of alanine aminotransferase measured 10 hrs after the first cerulein dose were significantly lower than in mice with pancreatitis treated with Ringer's lactate solution. In this model of acute pancreatitis, the same dosing regimen for ethyl pyruvate also ameliorated bacterial translocation to mesenteric lymph nodes and leakage of fluorescein isothiocyanate-labeled albumin from blood into bronchoalveolar lavage fluid. Treatment with ethyl pyruvate decreased pancreatic expression of tumor necrosis factor and interleukin-6 messenger RNA and nuclear factor-kappaB DNA binding in nuclear extracts prepared from pancreatic tissue.


CONCLUSIONS
Treatment with ethyl pyruvate ameliorated the local inflammatory response and decreased local and distant organ injury in a murine model of necrotizing pancreatitis.
Yang
Runkuan
R
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Uchiyama
Takashi
T
Alber
Sean M
SM
Han
Xiaonan
X
Watkins
Simon K
SK
Delude
Russell L
RL
Fink
Mitchell P
MP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011773:Pyruvates / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077325:Ringer's Lactate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007552:Isotonic Solutions; D011773:Pyruvates; D000077325:Ringer's Lactate; C046522:ethyl pyruvate