The aim of the present study was to compare the efficacy of a novel
phosphodiesterase 4 and 5 inhibitor,
LASSBio596, with that of
dexamethasone in a murine model of chronic
asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance), histology, and airway and lung parenchyma remodeling (quantitative analysis of
collagen and elastic fiber) were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the
asthma group (N = 9), mice were immunized with 10 microg
ovalbumin (OVA, ip) on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 microg OVA at 3-day intervals. Control mice (N = 8) received saline under the same protocol. In the
dexamethasone (N = 8) and
LASSBio596 (N = 8) groups, the animals of the
asthma group were treated with 1 mg/kg
dexamethasone disodium
phosphate (0.1 mL, ip) or 10 mg/kg
LASSBio596 dissolved in
dimethyl sulfoxide (0.2 mL,
ip) 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the
asthma group (77, 56, and 76%, respectively) compared to the control group. The
asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both
LASSBio596 and
dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion,
LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of
asthma.