Effects of corticosteroid or montelukast associated to iNOS inhibitior on inflammation and remodelling of distal lung in animals with chronic inflammation

Aims: Distal lung alterations have been recently addressed on asthma pathophysiology. We evaluated oxidative stress, actin content, IL5 and MMP9 positive cells in distal lung parenchyma after montelukast or dexamethasone treatments associated or not to an iNOS inhibitor (1400W) in guinea pigs (GP) with chronic inflammation. Methods: GP were inhaled with ovalbumin (OVA group-2x/week/4weeks). After 4th inhalation, GP were treated with montelukast (M group-10mg/kg/PO/day) or dexamethasone (D group-5mg/kg/IP/day). 1400W (W group-1mg/kg/day) was given daily in the last 4 days (W, DW and MW groups). After 72 hrs of 7th inhalation, GP were anesthetised, lung strips were submitted to histopathological evaluation. Results: Isoprostane was reduced in M (9.6±0.4%), D (7.4±0.2%), MW (6.1±0.1%), DW (5.5±0.2%) and W (6.9±0.4%) compared to OVA (14.5±0.2%, p<0.05). Actin content was attenuated in M (7.6±0.5%), D (6.3±0.2%), MW (6.2±0.4%), DW (5.4±0.2%) and W (5.7±0.2%) compared to OVA (9.6±0.5%, p<0.05). There was a decrease of IL5+ cells in W (4.9±0.5/10 4 μm 2 ), M (6.2±0.3/10 4 μm 2 ), D (4.8±0.3/10 4 μm 2 ), DW (2.8±0.2/10 4 μm 2 ), and MW (5.0±0.3/10 4 μm 2 ) compared to OVA (8.2±0.5/10 4 μm 2 , p<0.05). There was also a reduction of MMP9+ cells in M (6.4±0.4/10 4 μm 2 )), D (5.4±0.3/10 4 μm 2 ), MW (5.8±0.4/10 4 μm 2 ), DW (6.2±0.5/10 4 μm 2 ) and W (4.8±0.4/10 4 μm 2 ) compared to OVA (9.6±0.5/10 4 μm 2 , p<0.05). Conclusions: In this animal model, corticosteroid or montelukast associated to iNOS inhibitior contributes to the reduction of the oxidative stress, actin content, MMP9 expression and was efficient to attenuate Th2 cytokine expression in distal lung. Supported by: FAPESP, CNPq, LIM-20-HC-FMUSP.