title: Beneficial effects of nilotinib, tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats.
abstract: Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A.
authors: College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. Electronic address: manarahna@yahoo.com.
authors: Manar A
authors: MA
authors: Nader
authors: Department of Anatomy, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; Department of Histology & Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Ghalia M
authors: GM
authors: Attia
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D016572:Cyclosporine; D013482:Superoxide Dismutase; C498826:nilotinib
keywords: Apoptosis; Cyclosporine A; Free radical; Inflammation; Nephropathy; Nilotinib