title: Montelukast versus Dexamethasone Treatment in a Guinea Pig Model of Chronic Pulmonary Neutrophilic Inflammation.
abstract: Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours 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 tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil 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, significantly reduced specific airway resistance after the 9th LPS exposure, attenuated AHR to MCh, decreased LTB4 and increased HDAC activity in comparison to dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids.
authors.affiliation: a Department of Pharmacology , Ain Shams University , Egypt.
authors.forename: Hala S
authors.initials: HS
authors.lastname: Abdel Kawy
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D003521:Cyclopropanes; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D011804:Quinolines / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides; D011804:Quinolines; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D008315:Malondialdehyde; D003907:Dexamethasone; D006655:Histone Deacetylases; C093875:montelukast
keywords: COPD; Montelukast; dexamethasone; lipopolysaccharide