Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin.

ABSTRACT

OBJECTIVE: The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice. METHODS: CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule. RESULTS: CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)Hquinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice. DISCUSSION: In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy.