N-Acetylcysteine modulates acute lung injury induced by Pseudomonas aeruginosa in rats.
ABSTRACT 1. In critically ill patients, Pseudomonas aeruginosa-induced pneumonia and the lung injury associated with infection are major causes of mortality. The aim of the present study was to evaluate the protective properties of N-acetylcysteine (NAC) in rats infected with P. aeruginosa and the role of nitric oxide synthases (NOS) protein in this process. 2. Pneumonia was induced in rats by infecting them with P. aeruginosa intratracheally. One group of rats was treated with NAC (150 mg/kg per day, i.p., for 7 days). An untreated group served as the control. Samples were collected both before (0 h) and after infection (24 h). Bacterial loads in lung tissue, the lung wet : dry (W/D) ratio and pulmonary vascular permeability were assessed. Total cell and polymorphonuclear leucocyte cell counts in bronchoalveolar lavage fluid were determined. The expression of inducible (i) NOS and endothelial (e) NOS protein was analysed and correlated with indices of lung injury using Pearson's correlation analysis. 3. Bacterial load, lung injury indices and NOS expression increased after infection. Pretreatment with NAC mitigated lung injury although it did not significantly change bacterial loads. Furthermore, NAC treatment increased eNOS protein expression, but decreased iNOS expression, in lung tissues after infection. The expression of iNOS protein was positively correlated with indices of lung injury, whereas there was a negative correlation between eNOS expression and lung injury indices. 4. N-Acetylcysteine modulated P. aeruginosa-induced lung injury in rats. The results suggest that this effect maybe due to regulation of iNOS and eNOS protein expression by NAC.