title: Protective role of simvastatin on lung damage caused by burn and cotton smoke inhalation in rats.
abstract: 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 post-hoc 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 inhalation-associated lung dysfunction. However, the significant decrease in basal oxidant production may cause impairment in cellular signalling processes.
authors.affiliation: Department of General Surgery, Baskent University, Faculty of Medicine Ankara, Turkey. sedatbelli@hotmail.com
authors.forename: Sedat
authors.initials: S
authors.lastname: Belli
authors.forename: Ozgur
authors.initials: O
authors.lastname: Basaran
authors.forename: B Handan
authors.initials: BH
authors.lastname: Ozdemir
authors.forename: Suna
authors.initials: S
authors.lastname: Türkoğlu
authors.forename: Gülten
authors.initials: G
authors.lastname: Karabay
authors.forename: Altug
authors.initials: A
authors.lastname: Kut
authors.forename: Hamdi
authors.initials: H
authors.lastname: Karakayali
authors.forename: Mehmet
authors.initials: M
authors.lastname: Haberal
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000150:complications*; D032561:Cotton Fiber; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D015208:Smoke Inhalation Injury / Q000150:complications*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008315:Malondialdehyde; D019821:Simvastatin; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II