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

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive lung damage. A murine lung fibrosis model was developed by intra-tracheal instillation of bleomycin (BLM) (5 mg/kg, Once). Induction of lung fibrosis was characterized by means of pulmonary function assessment, serological assay of pro-inflammatory cytokines, histological scoring and collagen deposition, immuno-histochemical localization of IL-6 and TNF-Ü and RT-PCR quantification of pro-fibrotic growth factors; TGF-Ý, Ü-SMA, EGF-Ý and SMAD-3. BLM induced marked disruptions in all these aforementioned parameters. One of the current study aims was to evaluate the therapeutic effect of the combined therapy of the tyrosine kinase inhibitor, nintedanib (100 mg/kg, IP, Once daily, for 28 days)and Bone marrow-mesenchymal stem cells (BM-MSCs) (1{u00D7}106 cells/1ml/rat) on retraction of lung fibrosis in bleomycin treated rats.Treatment with either nintedanib or MSCs had almost the same beneficial effects in this traditional lung fibrosis model.The combination modality that incorporated both treatment options has proven therapeutic efficacy that outperformed either treatment given alone.A combined model was developed following administration of BLM and MD in an attempt to address as to whether or not carnitine deficiency would exacerbate the injurious effects of BLM on lung tissue.Interestingly, not only carnitine deficiency added to the detrimental toxic effects of BLM in lung tissue, but also BLM per se resulted in a sort of carnitine nadir.To resolve such paradox, one could argue that carnitine deficiency could possibly be a potential risk factor for inducing lung fibrosis

Issued also as CD