An Experimental Model to Induce Homogeneous and Progressive Pulmonary Fibrosis in Rats

Background: This study aims to develop a new experimental model of pulmonary fibrosis (PF) as an alternative to conventional bleomycin model to overcome its limitations and effectively screened the therapeutic agents. Similarity of new experimental model to human lung fibrosis particularly as uniform and continuous progression has encouraged us to evaluate the usefulness of this system by assessment of anti-fibrotic drug pirfenidone parallel with bleomycin induced PF. Materials and Methods: In new model, ovalbumin (OVA) related asthma induced rats were set to inhaled nebulized formaldehyde solution (0.5% v/v, 30 min) subsequent with cigarettes smoke exposure twice daily for 14, 28 or 42 days and designated as AFC treated rats. However, bleomycin (BLM) treated rats were administered (5 IU/kg) single dose intratracheal injection. The pulmonary associated effects were assessed through cells permeation study, biochemical evaluation, physical and physiological parameters, survival analysis and histopathological examination. Results: Overall, pulmonary associated effects induced by new as well as conventional bleomycin model exhibited almost similar results. Though, new model developed homogeneous and time dependent advancement in pulmonary severity with enhanced survival ratio as compared to bleomycin model. Comparatively, new model also represented low extent of normalization with pirfenidone treatment due to establishment of progressive fibrosis. Conclusion: This study reflects the role of formaldehyde and cigarette smoke in reinforcement of PF particularly during the lung inflammatory condition. Also, it provides novel idea to induce homogeneous and progressive PF in rats, which could resembles human lung fibrosis more specifically than conventionally induced by intratracheal bleomycin instillation.