title: Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment.
abstract: OBJECTIVE
  Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats.
  
  
  METHODS
  Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation.
  
  
  RESULTS
  The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions.
  
  
  CONCLUSIONS
  The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Ismael Francisco Mota Siqueira
authors.initials: IF
authors.lastname: Guarda
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Cristiano Jesus
authors.initials: CJ
authors.lastname: Correia
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Sueli Gomes
authors.initials: SG
authors.lastname: Ferreira
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ana Carolina Ramos
authors.initials: AC
authors.lastname: Moreno
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Marina Baquerizo
authors.initials: MB
authors.lastname: Martinez
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rocha-e-Silva
authors.affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004927:Escherichia coli Infections; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008642:Mesenteric Veins / Q000166:cytology / Q000187:drug effects*; D008833:Microcirculation; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D011773:Pyruvates; C046522:ethyl pyruvate