Background: Lung fibrosis is a progressive interstitial disease characterized by epithelial injury and excessive extracellular matrix deposition. Its pathogenesis involves oxidative stress, inflammation, fibroblast activation, and TGF-β1 signaling. Despite antifibrotic therapies, effective prevention of early fibrotic remodeling remains limited, necessitating novel or combined prophylactic approaches. Aim: This study aimed to evaluate the prophylactic effects of pirfenidone and azilsartan against amiodarone-induced lung fibrosis in rats, and to assess whether their combined use provides superior protection by targeting multiple pathological pathways. Methods: Forty-two rats were randomized into six groups: normal control, DMSO control, amiodarone fibrotic, pirfenidone prophylactic, azilsartan prophylactic, and combined pirfenidone + azilsartan. Pulmonary fibrosis was induced by oral amiodarone for 4 weeks. Pirfenidone and azilsartan were administered orally, alone or combined, over the same period. Outcomes included biochemical markers (MPO, hydroxyproline, TGF-β1, and p53) and histopathology with Ashcroft scoring, analyzed using ANOVA with post-hoc tests. Results: Amiodarone administration induced significant (p < 0.05) pulmonary injury, evidenced by increased levels of myeloperoxidase, hydroxyproline, transforming growth factor-β1, and p53 compared with controls, reflecting inflammation, collagen deposition, profibrotic signaling, and apoptosis. These changes were associated with marked histopathological alterations. Prophylactic treatment with pirfenidone or azilsartan significantly (p < 0.05) improved these parameters, indicating reduced inflammation and fibrosis. The combination therapy produced the greatest reductions in biochemical markers, the lowest Ashcroft score, and near-complete preservation of lung structure compared with either monotherapy. Conclusion: Pirfenidone and azilsartan exhibit significant prophylactic effects against amiodarone-induced lung fibrosis. Combination therapy provides the greatest protection, suggesting synergistic modulation. |
