BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in preterm infants. Montelukast, an effective cysteinyl leukotriene (cysLT) receptor antagonist, has a variety of pharmacological effects and has protective effects against a variety of diseases. Currently, the efficacy and safety of montelukast sodium in treating BPD has been revealed, however, the precise molecular mechanism of the effect of montelukast on BPD development remain largely unclear. Therefore, this study aimed to investigate the effect and mechanism of montelukast on BPD in vivo and in vitro.

MATERIAL AND METHODS: A mouse BPD model and hyperoxia-induced lung cell injury model were established and treated with montelukast. Then mean linear intercept (MLI), radial alveolar count (RAC), lung weight/body weight (LW/BW) ratio, pro-inflammatory factors, and oxidative stress-related factors in lung tissues were determined. Cell viability and apoptosis were detected using MTT assay and flow cytometer respectively.

RESULTS: The results showed that montelukast treatment relieved mouse BPD, evidenced by increased RAC and decreased MLI and LW/BW ratios. We also found that montelukast treatment reduced pro-inflammatory factors (TNF-α, IL-6, and IL-1β) production, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) content in the lung tissues of BPD mice. Besides, montelukast eliminated the reduced cell viability and enhanced cell apoptosis induced by hyperoxia exposure in vitro. Moreover, the upregulated pro-inflammatory factors production and p-p65 protein level in lung cells caused by hyperoxia were decreased by montelukast treatment.

CONCLUSIONS: Montelukast protected against mouse BPD induced by hyperoxia through inhibiting inflammation, oxidative stress, and lung cell apoptosis.

Keywords: Bronchopulmonary Dysplasia, Acetates, Animals, Newborn, Cyclopropanes, Hyperoxia, Interleukin-6, Lung, Lung Injury, Quinolines, Receptors, Leukotriene, Sulfides