title: Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals.
abstract: BACKGROUND
  Goblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.
  
  
  METHODS
  Male BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale.
  
  
  RESULTS
  Inflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57±1.30% for low dose; 1.50±0.93% for high dose versus 12.93±7.55%, P<0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45±0.30 for low dose; 0.81±1.00 for high dose versus 2.85±0.86 in the sensitized control group, P<0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1±0.43 versus 4.7±0.96, P<0.05 and 91.8±47.7 versus 14.8±4.6, P<0.01, respectively).
  
  
  CONCLUSIONS
  Verapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.
authors: Zakaria Research Center, Medical School of Islamic Azad University-Mashhad Branch, Mashhad, Iran.
authors: Mohammad Reza
authors: MR
authors: Khakzad
authors: Majid
authors: M
authors: Mirsadraee
authors: Amirhooshang
authors: A
authors: Mohammadpour
authors: Kamram
authors: K
authors: Ghafarzadegan
authors: Raziye
authors: R
authors: Hadi
authors: Mahdiye
authors: M
authors: Saghari
authors: Mojtaba
authors: M
authors: Meshkat
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000188:drug therapy / Q000503:physiopathology; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism; D006965:Hyperplasia; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D007371:Interferon-gamma; D014700:Verapamil