Endotoxin-induced acute lung injury is dependent upon oxidative response

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 L of saline) administered intratracheally (i.t.), LPS 6h (10 μg of LPS - i.t.), LPS 12h (10 μg of LPS - i.t.), LPS 24h (10 μg of LPS - i.t.), LPS 48h (10 μg of LPS - i.t.), LPS 24h (10 μg - i.t.) + NAC 40mg/kg (gavage) and 24h LPS (10 μg - i.t.) + NAC 100mg/kg (gavage). The antioxidant treatment protected the lungs from stress in the first 12h, but significant oxidative stress induction was observed at the 24-hour time point, and, after 48h, there was no protection exerted by the antioxidant treatment. NAC (N-acetylcysteine) reversed the elastance parameters, and ΔP1 and ΔP2 compared with 24h LPS alone. NAC reduced the number of inflammatory cells in histology analysis when compared with the 24h 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.