Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice

Abstract

Cyclophosphamide [CP], as alkylating agents has side effects such as nephrotoxicity. Cerium oxide nanoparticles [nanoceria; NC], as an antioxidant, are effective at reduction oxidative stress. This study evaluated the protective effect of nanoceria in nephrotoxicity induced CP. 32 BALB/c mice were randomly divided into four equal groups. Control, NC, CP and NC+CP. NC and CP injected intraperitoneally respectively in dose of 100 μg/kg for 3 days and 200 mg/kg single dose on 3th day of study. Two days after the final treatment, histochemical, serum biochemical, histopathological and immunohistochemical examinations were performed for determination effects of NC on nephrotoxicity. Oxidative stress and renal injury induced in CP treated mice were proved by the significantly elevation of urea and creatinine and alteration in oxidative stress markers [MDA and GSH levels]. Consequently, histopathological changes and apoptosis were markedly increased. NC was able to reduce MDA, urea, creatinine and increase GSH content. In addition, NC pretreatment could alleviated immunoreactivity of caspase-3. NC revealed a strong antioxidant in nephrotoxicity following CP treatment. This study suggests that NC through antioxidant and anti-apoptotic properties have protective effect against CP-induced nephrotoxicity.