Beneficial effects of nilotinib, tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats.
Int Immunopharmacol
; 33: 1-7, 2016 Apr.
Article
en En
| MEDLINE
| ID: mdl-26844915
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Inhibidores de Proteínas Quinasas
/
Riñón
/
Enfermedades Renales
/
Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2016
Tipo del documento:
Article