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 i.p.) on the development of shock caused by zymosan.


METHODS
Prospective, randomized study.


METHODS
University-based research laboratory.


METHODS
Male CD mice.


METHODS
Mice received either intraperitoneally zymosan (500 mg/kg, administered i.p. as a suspension in saline) or vehicle (0.25 mL/mouse saline). EP (75 mg/kg i.p. 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.


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-alpha, and interleukin-1beta 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-alpha, and interleukin-1beta 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.
Di Paola
Rosanna
R
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Mazzon
Emanuela
E
Genovese
Tiziana
T
Crisafulli
Concetta
C
Bramanti
Placido
P
Caminiti
Rocco
R
Esposito
Emanuela
E
Fink
Mitchell P
MP
Cuzzocrea
Salvatore
S
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D011773:Pyruvates / Q000627:therapeutic use*; D015054:Zymosan / Q000008:administration & dosage
D016207:Cytokines; D011773:Pyruvates; C046522:ethyl pyruvate; D015054:Zymosan