title: Effect of fudosteine, a cysteine derivative, on airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma.
abstract: OBJECTIVE
  Fudosteine is a cysteine derivative that is used as an expectorant in chronic bronchial inflammatory disorders. It has been shown to decrease the number of goblet cells in an animal model. This study examined the effects of fudosteine on airway inflammation and remodeling in a murine model of chronic asthma.
  
  
  METHODS
  BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA), and subsequently challenged with nebulized ovalbumin three days a week for four weeks. Seventy-two hours after the fourth challenge, airway hyperresponsiveness (AHR) and the cell composition of bronchoalveolar lavage (BAL) fluid were assessed. Fudosteine was administered orally at 10mg/kg or 100mg/kg body weight from the first to the fourth challenge.
  
  
  RESULTS
  We investigated the effects of fudosteine on the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenges. The administration of fudosteine during the challenge with ovalbumin prevented the development of airway hyperresponsiveness and accumulation of lymphocytes in the airways. Eotaxin, IL-4, and TGF-β levels and the relative intensity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) in BAL fluid were reduced by the fudosteine treatment; however, the number of eosinophils in BAL fluid and serum IgE levels did not change. The expression of TGF-β, the development of goblet cell hyperplasia, subepithelial collagenization, and basement membrane thickening were also reduced by the fudosteine treatment.
  
  
  CONCLUSIONS
  These results indicate that fudosteine is effective in reducing airway hyperresponsiveness, airway inflammation, and airway remodeling in a murine model of chronic asthma.
authors.affiliation: Field of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Ueno-Iio
authors.forename: Misako
authors.initials: M
authors.lastname: Shibakura
authors.forename: Koji
authors.initials: K
authors.lastname: Iio
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanimoto
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Kataoka
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D000485:Allergens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003553:Cystine; C113797:fudosteine