Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat

• Published in: Critical care medicine Vol. 34; no. 2; p. 471
• Main Authors: Ritter, Cristiane, da Cunha, Aline Andrea, Echer, Isabel Cristina, Andrades, Michael, Reinke, Adalisa, Lucchiari, Newton, Rocha, João, Streck, Emílio Luiz, Menna-Barreto, Sérgio, Moreira, José Cláudio F, Dal-Pizzol, Felipe
• Format: Journal Article
• Language: English
• Published: United States 01.02.2006
• Subjects: Acetylcysteine - pharmacology; Acetylcysteine - therapeutic use; Animals; Bronchoalveolar Lavage Fluid - chemistry; Deferoxamine - pharmacology; Deferoxamine - therapeutic use; Disease Models, Animal; Interleukin-1 - metabolism; Lipopolysaccharides - toxicity; Male; Oxidative Stress - drug effects; Rats; Rats, Wistar; Respiratory Distress Syndrome, Adult - drug therapy; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Distress Syndrome, Adult - pathology; Siderophores - pharmacology; Siderophores - therapeutic use; Tumor Necrosis Factor-alpha - metabolism; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use
• ISSN: 0090-3493
• DOI: 10.1097/01.CCM.0000199069.19193.89

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. Prospective, randomized, controlled experiment. Animal basic science laboratory. Male Wistar rats, weighing 200-250 g. 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. 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. 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.