Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 2 (2012), Issue 2, pp. 23-35 
doi:10.11131/2012/101337

Antiinflammatory Effect of Montelukast versus Dexamethasone on a COPD Model induced by Chronic Exposure to Lipopolysaccharide in Guinea Pigs

Background: Although corticosteroids are currently drugs of choice for anti-inflammatory therapy, the inflammatory process in chronic obstructive pulmonary disease (COPD) is essentially steroid- resistant. Aim: The aim of the present study was to assess the effects of oral treatment with montelukast (10 and 30mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS) in guinea pigs. Methods: Six groups of six male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5 & 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 h, 48 h apart with or without treatment with montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissues analyses were performed 48 hours after the final exposure to LPS(day20). Results: LPS-induced pulmonary dysfunction was associated with increase neutrophil count, leukotriene (LT) B4 and tumor necrosis factor (TNF)-α in BALF. Besides, there was a decreases in malondialdehyde (MDA) level and histone deacetylases(HDAC) activity in lung tissue. Inflammatory cells in lung parenchyma were also detected. Both montelukast (10 or 30 mg /kg) and dexamethasone reduced significantly neutrophils count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p<0.05). Montelukast, at a dose of 30 mg /kg, was effective in ameliorating the pulmonary dysfunction. This was evidenced by reducing specific airway resistance after the 9th LPS exposure, attenuating AHR to MCh, decreasing LTB4 and increasing HDAC activity. Conclusions: These results suggest that relieving inflammation with montelukast (30 mg /kg) can be useful as a therapeutic approach in chronic airway inflammatory diseases including COPD in a model of pulmonary neutrophilic inflammation poorly responsive to glucocorticoids.