Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin. (2nd November 2017)

• Record Type: Journal Article
• Authors: Basu, Abhishek; Bhattacharjee, Arin; Hajra, Subhadip; Samanta, Amalesh; Bhattacharya, Sudin
• Is Part Of: Redox report. Volume 22:Number 6(2017)
• Page Start: 377
• Page End: 387
• Publication Date: 2017-11-02
• Subjects: Vanadium -- kidney damage -- reactive oxygen species -- Nrf2/ARE pathway -- antioxidant enzymes -- apoptosis -- atomic absorption spectroscopy; Free radicals (Chemistry) -- Pathophysiology -- Periodicals; Oxidation, Physiological -- Periodicals; 541.224
• DOI: 10.1080/13510002.2016.1260192
• Languages: English
• ISSNs: 1351-0002

Abstract

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)H:quinone 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.