Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Pulmonary fibrosis is a chronic progressive and ultimately fatal lung disease. It is characterized by epithelial cell apoptosis, fibroblast proliferation and abnormal accumulation of extracellular matrix molecules, particularly collagen. Objective: The current study aimed to investigate the modulatory effects of pyrrolidinedithiocarbamate (PDTC; 100 mg/kg) and hesperidin (200 mg/kg) on bleomycin-induced pulmonary fibrosis (5 mg/kg; intratracheal) in rats. Materials and methods: Rats were randomly assigned to three groups: normal control, bleomycin control, PDTC-treated and hesperidin-treated groups. Lung injury was evaluated through histological examination, immunohistochemical detection of inducible nitric oxide synthase (iNOS) in lung tissue and evaluating the total and differential leucocytes count in bronchoalveolar lavage fluid. Lung tissue was used for biochemical assessment of lung content of hydroxyproline, transforming growth factor beta-1 (TGF-Ý1), tumor necrosis factor-alpha (TNF-Ü) as well as analysis of lipid peroxides, reduced glutathione (GSH), and total nitrite contents. Results: PDTC and hesperidin attenuated bleomycin-induced pulmonary fibrosis as evidenced by histological observations, decreased iNOS expression and prevention of bleomycin-induced altered total and differential leukocytes count. Additionally, PDTC and hesperidin caused a significant decrease in lung contents of hydroxyproline, TGF-Ý1, TNF-Ü, lipid peroxides, and total nitrite coupled with increase in lung GSH content as compared to bleomycin control group. Conclusion: PDTC and hesperidin attenuated bleomycin-induced pulmonary fibrosis in rats via its anti-inflammatory, antioxidant, and antifibrotic activities

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