Protective Role of Simvastatin on Lung Damage Caused by Burn and Cotton Smoke Inhalation in Rats

Background. Smoke inhalation injury is a major comorbid factor in patients with thermal injury and occurs in about 30% of patients with major burns. In addition, inhalation injury reportedly accounts for 20%-84% of the mortality in burned individuals and is associated with higher mortality rates for every age and burn size category. The aim of the present study was to investigate the effects of simvastatin on lung damage with burn and cotton smoke inhalation. Methods. Wistar rats were randomly assigned to three groups: saline treated control group, via an orogastric route (group 1, n = 6), burn (30%) and cotton smoke inhalated group (group 2, n = 6), and simvastatin treated (25 mg/kg/d, via an orogastric route) burn (30%) and cotton smoke inhalated group (group 3, n = 6). Rats were sacrificed at 48 h of the treatments and the trachea and lungs were removed completely. Tissue samples were taken for histopathologic, immunohistopathologic, and biochemical analyses. Univariate analysis of variance coupled with Duncan's posthoc test was performed for statistical evaluation. Results. Lung parenchymal and tracheoepithelial damage was confirmed in group 2 by histopathologic examination. Lung malonedialdehyde (MDA) levels were significantly decreased (P < 0.001), while glutathione (GSH) concentration did not alter in group 2 compared with group 1. Also, immunopathologic data revealed that epithelial iNOS level was elevated, while no modulation was detected in the level of myeloperoxidase (MPO). Simvastatin administration resulted in decreasing the lung parenchymal and tracheoepithelial damage. Tissue MDA levels were decreased significantly (P < 0.001), whereas GSH concentrations were elevated in group 3 compared with group 1 and group 2 (P < 0.001). Simvastatin treatment caused a decrease in epithelial iNOS levels, while MPO levels were not modulated. In addition, simvastatin significantly reduced pulmonary apoptosis in lung injury. Conclusions. Our results have indicated that simvastatin administration seems to play beneficial role in lung injury of rats promoted by combined burn and smoke inhalation. Thus, simvastatin may represent a potential approach to prevent smoke inhalationassociated lung dysfunction. However, the significant decrease in basal oxidant production may cause impairment in cellular signalling processes. (C) 2011 Elsevier Inc. All rights reserved.