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.

Keywords::

• Lipopolysaccharide
• oxidative stress
• acute lung injury
• pulmonary mechanics
• lung histology
• inflammatory response