Antioxidant Effect of Montelukast on Acute Lung Injury Induced by Lipopolysaccharide in Dogs

Abstract

BACKGROUND AND OBJECTIVE: Acute lung injury is characterized by accumulation of neutrophils in the lung, interstitial edema, and damage to the alveolar epithelium. Lipopolysaccharide (LPS) causes an inflammatory response and the release of reactive oxygen species and cellular and tissue damage to the lungs. Considering the role of oxidative stress in infections and proving the antioxidant properties of montelukast in several studies, the effect of montelukast on acute lung injury induced by lipopolysaccharide (as a model of infection) in dogs was investigated in this study. METHODS: In this experimental study, 20 healthy dogs (both male and female dogs of native breed with an average weight of 20 kg) were divided into four equal groups. The first group received oral montelukast (1 mg/kg), the second group received intravenous LPS (0.1 µg/kg), the third group received montelukast one hour before LPS and the fourth group received montelukast one hour after LPS. Bronchoalveolar lavage and blood sampling were performed at hour zero and 1.5 hours after the start of the test and the amount of malondialdehyde, catalase activity, glutathione peroxidase and total antioxidant capacity in serum and lavage fluid were measured using a kit. FINDINGS: LPS significantly increased malondialdehyde levels (from 10.5 to 139.8 μmol) and decreased catalase activity (from 0.018 to 0.007 μmol) (p= 0.0001), glutathione peroxidase (from 259 to 76.5 nmol) and the total antioxidant capacity (from 0.41 to 0.04 nmol) compared to hour zero. These changes were significantly adjusted by montelukast (p≤ 0.02). CONCLUSION: The results of this study showed that montelukast can enhance antioxidant defense against acute lung injury induced by LPS.

Keywords

• acute lung injury
• oxidative stress
• dogs
• lipopolysaccharide
• montelukast.