Nebivolol protects against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammation, and apoptosis.

Abstract

The usefulness of cyclophosphamide (CP) in the treatment of multiple human malignancies and immunological diseases is hindered by the danger of developing nephrotoxicity. The toxic metabolites of CP are suggested to be responsible for oxidative stress resulted from the production of reactive oxygen species (ROS) and stimulation of lipid peroxidation. Nebivolol (NEB) is a third-generation selective B1 adrenoceptor antagonist, but it has also various pharmacological properties such as anti-inflammation, anti-apoptotic, and antioxidant activities. Thus, the present study aims to explore the potential protective effect of NEB against CP-induced nephrotoxicity. A cumulative dose of CP (75mg/kg) was administered to albino rats by intraperitoneal injection. The protective effect of NEB was investigated by co-administration of NEB (10mg/kg orally daily). Administration of NEB with CP significantly improved renal functions and reduced the oxidative renal changes induced by CP injection. Co-administration of NEB ameliorated apoptosis and inflammatory markers that were markedly exaggerated by CP. Our results indicated that NEB could be used as a protective agent against CP-induced nephrotoxicity.