Ethyl pyruvate reduces the development of zymosan-induced generalized inflammation in mice

OBJECTIVE:: Ethyl pyruvate (EP) is a simple aliphatic ester, which has been shown to have anti-inflammatory effects in previous numerous cell culture and animal studies. In the present study, we investigated the effects of EP (75 mg/kg IP) on the development of shock caused by zymosan. DESIGN:: Prospective, randomized study. SETTING:: University-based research laboratory. SUBJECTS:: Male CD mice. INTERVENTIONS:: Mice received either intraperitoneally zymosan (500 mg/kg, administered IP as a suspension in saline) or vehicle (0.25 mL/mouse saline). EP (75 mg/kg IP was administered 1 and 6 hrs after zymosan administration. Organ failure and systemic inflammation in mice was assessed 18 hrs after administration of zymosan and/or EP. MEASUREMENTS AND MAIN RESULTS:: Treatment of mice with EP attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. EP also attenuated the lung, liver, and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase activity in the lung and intestine caused by zymosan. Immunohistochemical analysis for inducible nitric oxide synthase, nitrotyrosine, poly (ADP-ribose), tumor necrosis factor-α, and interleukin-1β revealed positive staining in pancreatic and intestinal tissue obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, inducible nitric oxide synthase, poly (ADP-ribose), tumor necrosis factor-α, and interleukin-1β were markedly reduced in tissue sections obtained from zymosan-injected mice, which had received EP. In addition, administration of zymosan caused a severe illness in the mice characterized by a systemic toxicity, significant loss of body weight, and a 60% of mortality at the end of observation period (7 days). Treatment with EP significantly reduced the development of systemic toxicity, the loss in body weight, and the mortality (20%) caused by zymosan. CONCLUSIONS:: This study provides evidence that EP attenuates the degree of zymosan-induced shock in mice.