title: Endotoxin-induced acute lung injury is dependent upon oxidative response.
abstract: The aim of the present study was to investigate the involvement of oxidative stress in acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects upon cell structure, function and inflammation. In total, 108 male C57BL/6 mice were divided into seven groups: CTR Group (50 µL of saline) administered intratracheally (i.t.), LPS 6 h (10 µg of LPS - i.t.), LPS 12 h (10 µg of LPS - i.t.), LPS 24 h (10 µg of LPS - i.t.), LPS 48 h (10 µg of LPS - i.t.), LPS 24 h (10 µg - i.t.) + NAC 40 mg/kg (gavage) and 24 h LPS (10 µg - i.t.) + NAC 100 mg/kg (gavage). The antioxidant treatment protected the lungs from stress in the first 12 h, but significant oxidative stress induction was observed at the 24-hour time point, and, after 48 h, there was no protection exerted by the antioxidant treatment. NAC (N-acetylcysteine) reversed the elastance parameters, and ΔP1 and ΔP2 compared with 24 h LPS alone. NAC reduced the number of inflammatory cells in histology analysis when compared with the 24 h LPS alone-treated group. NAC also inhibited the transcription of NFκB, IL-6, TNF-α and COX2 usually induced by LPS. Our results suggest that oxidative stress plays an important role in structural, functional and inflammatory responses in the ALI model.
authors: Laboratório de Reparo Tecidual - DHE/IBRAG/UERJ, Rio de Janeiro, Brazil.
authors: Eduardo Tavares
authors: ET
authors: Lima Trajano
authors: Cinthya
authors: C
authors: Sternberg
authors: Maurício
authors: M
authors: Caetano
authors: Marco Aurélio
authors: MA
authors: Santos Silva
authors: Luís Cristóvão
authors: LC
authors: Porto
authors: Juliana Carvalho
authors: JC
authors: Santos
authors: Marcelo Lima
authors: ML
authors: Ribeiro
authors: Clarissa Bichara
authors: CB
authors: Magalhães
authors: Walter Araújo
authors: WA
authors: Zin
authors: Cláudia Farias
authors: CF
authors: Benjamim
authors: Samuel Santos
authors: SS
authors: Valença
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine