The Effect of Post-leTreatment N-Acetylcysteine in LPS-Induced Acute Lung Injury of Rats

Abstract

Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor a (TNF-alpha) and interleukin 1 beta (IL-1 beta) were measured in BALF. Nuclear factor gamma B (NF-kappa B), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-a and IL-1 beta concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5 +/- 2.8 nmol/mL vs. 16.5 +/- 1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4 +/- 1.8 unit/g vs. 11.2 +/- 6.3 unit/g, tissue) (p<0.048). The concentration of NF-kappa B in NAC treatment group was significantly lower than that of LPS group (0.3 +/- 0.1 ng/mu L vs. 0.4 +/- 0.2 ng/mu L) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-kappa B activation.