title: Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat.
abstract: OBJECTIVE
  Interventions that reduce the generation or the effects of reactive oxygen species exert controversial effects in animal models of lung injury, and these could be secondary to the pro-oxidant effects of antioxidants generally by their interaction with iron. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of acute lung injury induced by intratracheal lipopolysaccharide injection.
  
  
  METHODS
  Prospective, randomized, controlled experiment.
  
  
  METHODS
  Animal basic science laboratory.
  
  
  METHODS
  Male Wistar rats, weighing 200-250 g.
  
  
  METHODS
  Rats exposed intratracheally to lipopolysaccharide were treated with N-acetylcysteine (20 mg/kg subcutaneously 3, 6, and 12 hrs after lipopolysaccharide instillation), deferoxamine (20 mg/kg subcutaneously 3 hrs after lipopolysaccharide instillation), N-acetylcysteine (20 mg/kg, 3, 6, and 12 hrs after lipopolysaccharide instillation) plus deferoxamine (20 mg/kg 3 hrs after lipopolysaccharide instillation), or vehicle.
  
  
  RESULTS
  Acute lung injury was induced by intratracheal instillation of lipopolysaccharide in Wistar rats. The animals were randomly divided into five groups: group 1, control with instillation of isotonic saline; group 2, lipopolysaccharide treated with saline; group 3, lipopolysaccharide treated with N-acetylcysteine; group 4, lipopolysaccharide treated with deferoxamine; and group 5, lipopolysaccharide treated with N-acetylcysteine plus deferoxamine. Several times after lipopolysaccharide instillation, the rats were killed and a bronchoalveolar lavage was performed to determine thiobarbituric acid reactive species, protein carbonyls, superoxide dismutase and catalase activities, mitochondrial superoxide production (oxidative stress variables), the degree of the alveolar-capillary membrane compromise, and inflammatory infiltration. Samples from the lung were isolated and assayed for oxidative stress variables or histopathologic analyses. N-acetylcysteine plus deferoxamine decreased bronchoalveolar lavage fluid protein, inflammatory cells, oxidative damage variables, and proinflammatory cytokines. N-acetylcysteine plus deferoxamine treatment significantly attenuated lung oxidative damage, mitochondrial superoxide production, and histopathologic alterations after lipopolysaccharide instillation.
  
  
  CONCLUSIONS
  Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine decreases oxidative stress and mitochondrial dysfunction and limits inflammatory response and alveolar pathology induced by lipopolysaccharide in the rat.
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Ritter
authors.forename: Aline Andrea
authors.initials: AA
authors.lastname: da Cunha
authors.forename: Isabel Cristina
authors.initials: IC
authors.lastname: Echer
authors.forename: Michael
authors.initials: M
authors.lastname: Andrades
authors.forename: Adalisa
authors.initials: A
authors.lastname: Reinke
authors.forename: Newton
authors.initials: N
authors.lastname: Lucchiari
authors.forename: João
authors.initials: J
authors.lastname: Rocha
authors.forename: Emílio Luiz
authors.initials: EL
authors.lastname: Streck
authors.forename: Sérgio
authors.initials: S
authors.lastname: Menna-Barreto
authors.forename: José Cláudio F
authors.initials: JC
authors.lastname: Moreira
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D017262:Siderophores; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D003676:Deferoxamine; D000111:Acetylcysteine