Experimental Model Of Papain-induced Pulmonary Emphysema

Abstract

Chronic obstructive pulmonary disease (COPD) typical features may be induced by administration of exogenous proteases, Rationale: such as papain. Despite the extensive description of the cellular and molecular aspects involved, much remains to be explored in these models.To disclose a putative gender-related pulmonary functional response in a mice model of papain-induced emphysema. Aim:30 male (M) and female (F) BALB/c mice (20-25 g) were randomly divided into four groups. The animals received Materials and methods: intratracheally 50 μL of saline (groups SALF and SALM) or 0.2 U/μL of papain diluted in 50 μL of saline (groups PAPF and PAPM) once a week, for 2 weeks. The animals were weighed once a week. 2 wks after the last intratracheal instillation, the animals were sedated, anesthetized and paralyzed. Lung mechanics (resistive, viscoelastic and total pressures, static elastance and elastic component of viscoelasticity) were measured. The lungs were prepared for histology and biochemical tests were run to evaluate oxidative stress.Pulmonary functional changes were more pronounced in males, with increased elastic, resistive and viscoelastic components of Results: pulmonary mechanics: Est (SALM 19.7 ± 1.7; PAPM 25.5 ± 1.4 cmH O/ml), ΔP1 (0.43±0.04; 0.76 ±0.03 cmH O), ΔP2 (0.94 ±0.08; 1.23 ±0.06 2 2 cmH O), ΔE (4.7± 0.4; 6.2±0.3 cmH O/ml), while females showed only higher elastic and resistive components: Est (SALF 21.9±1.7; PAPF 2 2 29.6±1.4), ΔP1 (0.50±0.04; 0.67±0.03). Increased influx of polymorphonuclear cells was detected in lung parenchyma. The reduction in collagen and elastic fibers confirmed a serious injury at 14 days after exposure. Males presented increase significantly higher in functional residual capacity (SALM 0.20±0.01; PAPM 0.41±0.02 ml) and mean alveolar diameter (SALM 39.4±0.7; PAPM 58.8±0.6 mm), than females (SALF 0.21±0.02; PAPF 0.29±0.01 ml) and (SALF 37.61±0.7; PAPF 47.27±0.6ï€ mm). Male and female mice exposed to papain gained weight to a lesser extent. Antioxidant enzymes were altered suggesting the existence of a mechanism for pulmonary defense against reactive oxygen species. Papain impaired respiratory system functional and inflammatory profiles, and induced oxidative stress. Conclusions:Males displayed more severe lung injuries than females.FAPERJ, CNPq, PRONEX, MCT.