Possible Protective Role of Pirfenidone Versus Combined Antifibrotic Therapy Colchicine and Pirfenidone in a Rat Model of Bleomycin Induced Pulmonary Fibrosis and Evaluation of their Potential Impact on α-SMA, IL6 and TGFβ (Histological and Immunohistochemical Study)

Introduction: Combined antifibrotic treatment strategy in the management of pulmonary fibrosis attracts the attention worldwide especially after COVID-19 pandemic and still a point of recent research work.
Aim of the Work: This study intended to clarify the possible protective serve of Pirfenidone only versus combined antifibrotic action of both pirfenidone and colchicine in a bleomycin created pulmonary fibrosis rat model.
Materials and Methods: Forty adult albino male rats were partitioned equally into four groups. Control group I. Bleomycin-treated group II: (10mg/kg/d by intraperitoneal injection for the first 5 days of the experiment). Pirfenidone-treated group III: (100mg/kg/d orally). Combined pirfenidone and colchicine-treated group IV: (oral pirfenidone 100mg/kg/d + oral colchicine 0.5mg/kg/d for 30 days in the created pulmonary fibrosis model).
Results: Histopathological results of group II revealed marked distortion of the bronchiolar mucosal lining and the alveolar system. Mast cells appeared infiltrating the pulmonary interstitium. Multiple lamellar bodies appeared in pneumocyte type I and II. Moreover, the myofibroblasts appeared in large number in the interalveolar septa. There was significant increase in the immune staining areas of both α-SMA, IL6 and the collagen deposition between group II and group I. Dramatic rise in serum concentrations of TGβ, IL6, MDA and SOD compared to the control group. Group III showed moderate improvement of histopathological and immunohistochemical findings as well as the collagen deposition and serum inflammatory markers were decreased significantly between groups III and II. The best results were observed in group IV, a significant fall in the immunostaining areas of both α-SMA and IL6 and marked decrease of serum levels of SOD and MDA levels between group IV and groups III and II.
Conclusion: Combined antifibrotic therapy offered remarkable improvement in the architecture of the pulmonary tissue. There was substantial improvement in the histopathological and immunohistochemical features in the combined group in comparison with pirfenidone treated group.