Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study

Abstract

Background: Different medical therapies are employed in acute lung injury (ALI) but there is still a debate about the efficacy of these drugs. Among these therapies steroids are clinically applied and bosentan is experimentally studied. The aim of this study was to evaluate the efficacy of these two drugs to treat inflammation in ALI by histopathological comparison. Methods: The five experimental groups (n = 5 per group) were: saline control (Group I); lipopolysaccharide (LPS) + saline (Group II); LPS + dexamethasone (Group III); LPS + 50 mg/kg bosentan (Group IV); and LPS + 100 mg/kg bosentan (Group V). Bosentan was administered orally one hour before and 12 hours after LPS treatment. Dexamethasone was administered intraperitoneally in three doses of 1 mg/kg; one dose was co-administered with LPS and the other two doses were given respectively 30 minutes before and after LPS treatment. Vasodilation-congestion, hemorrhage, polymorphonuclear leukocyte (PMN) infiltration, mononuclear leukocyte (MNL) infiltration, alveolar wall thickening, alveolar destruction/emphysematous appearance, and focal organization were the parameters used as criteria for evaluating inflammation and efficacy of treatment. Results: Compared to the LPS-only group (Group II), dexamethasone treatment (Group III) resulted in significant improvements in vasodilation-congestion, hemorrhage, PMN and MNL infiltration, alveolar wall thickening and emphysematous areas. Treatment with 50 mg/kg dose of bosentan (Group IV) also resulted in significant improvements in hemorrhage, PMN and MNL infiltration, alveolar wall thickening and alveolar destruction. Reducing lung injury and reparative effects of 100 mg/kg bosentan were significant in all parameters. Conclusions: Bosentan is as effective as dexamethasone for treating lung injury in ALI. Bosentan at 100 mg/kg can be recommended as a first treatment choice based on its significant reducing lung injury and reparative effects.