Effect of proteinase inhibitor from crataeva tapia (cratabl) in distal lung mechanical, inflammatory and remodeling alterations induced by elastase in mice

Aims: The leading role of elastase in the emphysema physiopathology has been recognized. The present study aimed to evaluate if a plant proteinase inhibitor CratabL contributes to inactivation of elastase-induced mechanical, inflammatory and extracellular matrix remodelling alterations. Methods: C57Bl6 mice received elastase intranasally (50ml/animal E group). Control group received saline (Ve group). Afterwards, mice were treated with CratabL (2mg/kg) at days 1, 15, 21, 28, 35 after elastase instillation (I-E group). At day 40, mice were anesthetized and mechanically ventilated and we analyzed respiratory system resistance and elastance, tissue elastance, tissue damping and airway resistance. Afterwards, BAL was performed and lungs were removed. By morphometry, we quantified the mean linear intercept (Lm) and the collagen and elastic fibers in distal lung parenchyma. Results: We did not observe any differences in pulmonary mechanics comparing all groups. In E group, there was an increase in BAL-total cells, BAL-lymphocytes, BAL-neutrophils, collagen and elastic fibers and Lm compared to Ve group (p<0.05). The CratabL treatment in elastase treated animals decreased Lm (105.9±10.0μm) compared to E group (p<0.05). BAL-neutrophils (7.2±1.4×10 4 cells/mL), and collagen content (0.59±0.02%) were decreased in I-E group compared to E animals (p<0.05). Conclusions: This plant proteinase inhibitor ( CratabL ) reduced elastase-induced pulmonary inflammatory and remodeling alterations which may be considered as a new and potential therapeutic strategy for COPD treatment. Financial support: FAPESP, CNPq, LIM- HCFMUSP.