title: Ethyl pyruvate reduces the development of zymosan-induced generalized inflammation in mice.
abstract: 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.
authors.affiliation: IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Rocco
authors.initials: R
authors.lastname: Caminiti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: 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
chemical_list: D016207:Cytokines; D011773:Pyruvates; C046522:ethyl pyruvate; D015054:Zymosan