Protective effect of leukotriene receptor antagonist montelukast on smoking-induced lung injury in Wistar rats.
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.
Yüksel
Hasan
H
Department of Pediatrics, Celal Bayar University Medical Faculty, Manisa 45020, Turkey. hyukselefe@hotmail.com
Ozbilgin
Kemal
K
Coskun
Senol
S
Tuglu
Ibrahim
I
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D003521:Cyclopropanes; D005260:Female; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000009:adverse effects*; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D020011:Protective Agents; D011804:Quinolines; D013440:Sulfides; C093875:montelukast