montelukast and Lung-Diseases

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.

Topics: Acetates; COVID-19; COVID-19 Drug Treatment; Cyclopropanes; Cytokine Release Syndrome; Humans; Leukotriene Antagonists; Leukotrienes; Lung Diseases; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides

Increased activation of alveolar macrophage, neutrophil and mast cell has been proven in cigarette smoking (CS)-related lung disorders (CSLD). An increased production of cysteinyl-leukotrienes (LTs), which are mediators secreted from the mentioned cells, in response to CS has been shown in humans. The protective effect of LT1 receptor-1 antagonist (LTR-1AT) on CSLD is, however, not known. In this study we aimed to determine whether there is any protective effect of a LTR-1AT, montelukast (MK), on CSLD in Wistar rats. Nine controls and twenty-three smoke-exposed rats were enrolled into this study. Controls were exposed to non-filtered air, and the smoke-exposed rats were exposed to CS for 6 h/day, 6 days/week for three weeks. The CS-exposed rats were also treated with 0.1 mg/kg/day of MK or saline. Morphometric criteria for lung injury were determined as the mean linear intercept of alveolar septa (Lm), the volume density of alveolar septa (Vvspt) and the density of the alveolar surface area per unit volume of lung parenchyma (Sva.pa). Lung mast cells (LMC), which are a major source of LTs, were also counted. Results showed that Lm of the control group was significantly lower and Vvspt, Sva.pa of the controls were significantly higher compared to those of the CS-exposed groups. Animals treated with MK had significant protection against CSLD. Lm was significantly higher and Vvspt, Sva.pa were lower in the saline group than in the MK-treated group. The number of LMC in the CS-exposed groups was also significantly higher than that in the control group. Based on these results, one can suggest that some part of the pathogenesis of CSLD may be related to an enhanced LTs synthesis and LTR-1AT. Therefore, montelukast may protect against active or passive smoking-induced lung injury and related disorders.

Topics: Acetates; Animals; Cyclopropanes; Female; Leukotriene Antagonists; Lung Diseases; Macrophages, Alveolar; Mast Cells; Protective Agents; Quinolines; Rats; Rats, Wistar; Smoking; Sulfides