Effect of Pirfenidone on Bleomycin Induced Pulmonary Alveolar Fibrosis in Adult Male Rats (Histological, Immunohistochemical, Morphometrical and Biochemical Study)

Introduction: Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as Hodgkin’s lymphoma. The major limitation of bleomycin therapy is the pulmonary toxicity. Pirfenidone is a modified phenyl pyridine that has an antioxidant, anti-transforming growth factor and anti-platelet derived growth factor effects. Aim of the study: to evaluate the histological, immunohistochemical and biochemical changes in the pulmonary alveoli of adult male albino rats after intake of bleomycin and the possible role of pirfenidone in minimizing these changes. Material and Methods: Forty adult male albino rats were used in this study. They were divided equally into 4 equal groups; the first group (control), the second group that received bleomycin for 10 days, the third group that received pirfenidone for 10 days and the fourth group that received pirfenidone & bleomycin for 10 days. The lungs were dissected out, processed and lung sections were stained with Hx&E, Masson's trichrome and immunohistochemicaly. Then they were examined by light microscope for histological and immunohistochemical study to evaluate the structure of pulmonary alveoli. Biochemical measurement of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and tumor necrosis factor-α (TNF-α) were also performed. Results: Bleomycin treatment in the second group induced alveolar inflammation, interstitial pulmonary inflammation and pulmonary alveolar fibrosis, while pirfenidone significantly reduced these induced lung injuries in the fourth group rats that treated with pirfenidone and bleomycin. These protective effects were associated with a significant (P<0.05) reduction in the levels of MDA, and TNF-α associated with a significant (P<0.05) increase in the levels of GSH-P in the homogenate of lung tissue compared with the second group. Conclusion: The present study showed a protective effect of pirfenidone on the structure of pulmonary alveoli subjected to bleomycin intake. So intake of pirfenidone with bleomycin is advised for treatment of pulmonary alveolar toxicity.