Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms

Abstract

BackgroundBronchopulmonary 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/MethodsA 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.ResultsThe 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.ConclusionsMontelukast protected against mouse BPD induced by hyperoxia through inhibiting inflammation, oxidative stress, and lung cell apoptosis.

As a potential treatment of COVID-19: Montelukast

“…Then, leukocytes accumulating in the lungs are activated and secretive reactive oxygen species and proteases that damage capillary endothelium and alveolar epithelium. Montelukast therapy has been shown in recent studies to reduce TNF-α, IL-6 and IL-1b levels [3,4]. The pronounced inhibitory effect of montelukast against bradykinin-induced tracheal smooth muscle contraction has also been demonstrated, which supports the interaction between bradykinin and leukotriene mediators [3,6].…”

“…In addition, as it is known, COVID-19 reaches the cell through angiotensin-converting enzyme (ACE) receptors and leads to severe pneumonia and thus increased mortality rates during infection by binding to human ACE2 [3,4]. The cough that can develop with ACE inhibition is caused by increased bradykinin and its bronchoconstrictor effect, and montelukast, a selective LTD4 antagonist, has an inhibitory effect on bradykinin-induced airway hypersensitivity [5,6].…”

The assessment of the serum levels of TWEAK and prostaglandin F2α in COVID – 19

“…It is claimed that montelukast, a potent cysteinyl leukotriene receptor antagonist, can be a potential therapeutic agent in COVID -19 [29]. Montelukast suppresses leukotrienemediated inflammatory response by inhibiting the binding of leukotrienes to the receptor [30]. The most important cause of COVID -19 related deaths is ARDS.…”

Potential antiviral and anti-inflammatory role of Montelukast in viral infections including SARS-CoV-2 Infection (COVID19) – A Descriptive review

“…These activated leukocytes then secrete proteases and reactive oxygen species (ROS) that lead to capillary and alveolar damage, which is responsible for the leaky capillaries [31]. Treatment with montelukast has found to decrease these afore mentioned inflammatory cytokines and markers of oxidative stress like malondialdehyde (MDA) in some animal models [32].…”

“…Montelukast use blocks all the above activities [61]. Recent studies have shown that Montelukast can lower elevated levels of IL-1b, IL-6, IL-8, TNF-Alpha [32,38]. Montelukast also demonstrated a prominent inhibitory effect on bradykinin mediated tracheal smooth muscle contraction, which could be related to leukotriene interaction [40].…”