Effects of acetylsalicylate overdose on lipopolysaccharide-induced lung injury in rats: the role of the VEGF

Abstract

Aim: Vascular endothelial growth factor production is decreased depending on the alveolar epithelial cell damage. Acute over expression of vascular endothelial growth factor in lung tissue contributes to the formation permeability. Excessive doses of acetylsalicylate (ASA) may induce pulmonary edema by increasing pulmonary vascular permeability. In this study, the effects of acetylsalicylate overdoses were evaluated on bronchoalveolar lavage fluid levels of vascular endothelial growth factor in the presence of lipopolysaccharide-induced lung injury in rats. Materials and Methods: Lung injury was induced by intraperitoneal injection of lipopolysaccharide (LPS). Rats were divided into six different sets consisting of 7 rats each for control, ASA-300, ASA-500, LPS, LPS+ASA-300 and LPS+ASA-500 series. ASA, 300 mg and 500 mg/kg doses were given by gavage. Acetylsalicylate was given 24 hours after lipopolysaccharide injection in LPS+ASA groups. Rats were sacrificed 6 hours after acetylsalicylate administration and bronchoalveolar lavage was performed. Results: In bronchoalveolar lavage fluid, vascular endothelial growth factor, matrix metalloproteinase-2 and nitric oxide levels were increased in group of ASA-500, and were decreased in groups of LPS+ASA. In addition, plasma salicylate half-life was prolonged in LPS+ASA groups. Conlusion: Lipopolysaccharide increases the time of being metabolized of acetylsalicylate. The lung tissue damage increases due to vascular endothelial growth factor, matrix metalloproteinase-2 and nitric oxide related mechanisms and recovery period is affected adversely. Also in humans, severe toxic effects on the lung tissue that can be generated by 300 and 500 mg/kg acetylsalicylate doses in rats showed less toxic effect.