Abstract
This study investigated the effects of LASSBio596, a phosphodiesterase types 4 and 5 inhibitor, in a murine model of chronic asthma. Twenty-four BALB/c mice were randomly divided into four groups. In asthma group mice were sensitised to ovalbumin (10 μg, i.p.) using an adjuvant-free protocol, and challenged by multiple intratracheal instillations of ovalbumin. Twenty-four hours before the first intratracheal instillation, dexamethasone (1 mg.kg-1) or LASSBio596 (10 mg.kg-1) was intraperitoneally injected daily for eight days. Sham mice received saline using the same protocol. Twenty-four hours after the last intratracheal instillation, lung mechanics (airway resistance, viscoelastic pressure, static elastance) and histology (morphometry, quantitative analysis of collagen and elastin) were computed. Airway resistance (112%), viscoelastic pressure (80%) and static elastance (83%) increased significantly in asthma group. Asthma group presented alveolar collapse, bronchoconstriction, a marked eosinophilic infiltration, and fibrosis in alveolar walls and airways. Fragmented elastic fibre was showed in airways. Both LASSBio596 and dexamethasone avoided the changes in lung mechanics, inhibited eosinophilic recruitment, bronchoconstriction, and fibroelastogenesis. In conclusion, LASSBio596 modulated lung inflammation and remodelling and is as efficacious as dexamethasone in treating asthma.
Supported by: PRONEX, FAPERJ, CNPq