title: Effects of glycine, pyruvate, resveratrol, and nitrite on tissue injury and cytokine response in endotoxemic rats.
abstract: BACKGROUND
  Glycine, pyruvate, resveratrol, and nitrite are well-known protective compounds among others in ischemic tissue injury. Here, we compared their effects in acute lipopolysaccharide (LPS)-induced shock in rats to assess whether inhibition of the proinflammatory cytokine response is a prerequisite for their protective actions.
  
  
  METHODS
  Rats (six or eight per group) were anesthetized, received LPS as an intravenous bolus (2.5 mg/kg), and were observed for 5 h. Glycine, sodium pyruvate, resveratrol, and sodium nitrite were continuously infused starting 30 min before LPS administration. Parameters included histopathologic changes, organ-specific cytokine levels, plasma nitrite and nitrate concentrations, and time courses of biomonitoring parameters, marker enzyme activities, and plasma cytokine concentrations.
  
  
  RESULTS
  Glycine, pyruvate, resveratrol, and nitrite enhanced arterial blood pressure after LPS-induced shock. Also, parameters reflecting tissue ischemia were significantly improved and plasma markers of organ injury ameliorated by all substances. Of the plasma cytokine concentrations increased by LPS, some were differently decreased or even further increased by the substances. None of them reduced the elevated plasma nitrite and nitrate concentration. Glycine diminished the increases in tissue cytokine levels organ specifically, pyruvate decreased some cytokine concentrations in all organs, and nitrite significantly affected only a few cytokine concentrations in some organs, whereas the levels of many cytokines were raised by resveratrol. All substances except resveratrol decreased granulocyte infiltrates in the liver.
  
  
  CONCLUSIONS
  The present results demonstrate that glycine, pyruvate, resveratrol, and nitrite protect against LPS-induced shock and tissue injury (cell death) in rats and suggest that inhibition of the proinflammatory cytokine response is not mandatory for their protective actions.
authors: Institut für Physiologische Chemie, Universitätsklinikum, Universität Duisburg-Essen, Essen, Germany.
authors: Tim
authors: T
authors: Hamburger
authors: Martina
authors: M
authors: Broecker-Preuss
authors: Matthias
authors: M
authors: Hartmann
authors: F Ulrich
authors: FU
authors: Schade
authors: Herbert
authors: H
authors: de Groot
authors: Frank
authors: F
authors: Petrat
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004573:Electrolytes / Q000097:blood; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005998:Glycine / Q000008:administration & dosage*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D019289:Pyruvic Acid / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D004573:Electrolytes; D006454:Hemoglobins; D008070:Lipopolysaccharides; D013267:Stilbenes; D019289:Pyruvic Acid; D012977:Sodium Nitrite; D000077185:Resveratrol; D005998:Glycine