Hussam AS Murad
King Abdulaziz University, Saudi Arabia
Title: Impact of combined inhalation of Roflumilast or formoterol plus fluticasone on matrix metalloproteinase-9 and its inhibitor in ovalbumin-asthmatic mice
Biography
Biography: Hussam AS Murad
Abstract
Statement of the Problem: In a recently-published work, we concluded that co-inhalation of roflumilast+fluticasone more significantly improved inflammatory and histopathological changes than co-inhalation of formoterol+fluticasone in ovalbumin-asthmatic mice. The matrix metalloproteinase-9 (MMP-9) is the principal MMP involved in pathogenesis of asthma, and thus its inhibition could be beneficial to protect against airway inflammation and remodeling. This study was designed in ovalbumin-asthmatic mice to investigate effects of inhaled roflumilast and formoterol alone or combined with fluticasone on levels of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF).
Methodology & Theoretical Orientation: Asthma was induced in female BALB/c mice by ovalbumin sensitization and challenge. In addition to the normal control (NC) group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n=8): positive control (PC), vehicle-treated, and five drug-treated groups. Treatments (μg/kg) were given as 15 min-inhalation once/day for seven days as follows: roflumilast (R, 500), formoterol (Fo, 50), fluticasone (F, 1000), roflumilast+fluticasone (R+F, 500+1000), and formoterol+fluticasone (Fo+F, 50+1000).
Findings: The PC mice showed significant increases of the levels of MMP-9 and TIMP-1 in the BALF compared to the NC group. All treatments (except formoterol) significantly decreased these ovalbumin-induced changes mainly with the R+F group which showed a non-significant difference from the NC group. The combinations were significantly different from monotherapies and the R+F group was significantly different from the Fo+F group.
Conclusion & Significance: Co-inhalation of roflumilast+fluticasone more significantly improved the BALF levels of MMP- 9 and TIMP-1 than co-inhalation of formoterol+fluticasone in the ovalbumin-asthmatic mice. Recommendations of adding inhaled roflumilast to inhaled corticosteroids could be beneficial in treatment of asthma due to its antiinflammatory and antifibrotic effects.