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)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.

KEYWORDS:

• Vanadium
• kidney damage
• reactive oxygen species
• Nrf2/ARE pathway
• antioxidant enzymes
• apoptosis
• atomic absorption spectroscopy

Acknowledgement

The authors appreciate the help from Dr Syamsundar Mandal, Department of Epidemiology and Biostatistics, Chittaranjan National Cancer Institute for his guidance on the statistical analysis of this study. The authors wish to thank the Prof (Dr) Jaydip Biswas, Director, CNCI for the support in this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Abhishek Basu is the Research Associate (RA) in the Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India awarded by Council of Scientific and Industrial Research (CSIR), New Delhi, India. His areas of expertise are pharmacology, toxicology and cancer biology. His research work deals with the evaluation of organovanadium compounds as a suitable chemoprotectant and sensitizing agent in cancer chemotherapy in order to establish a better chemotherapeutic regimen with the aim to improve patients’ quality of life.

Arin Bhattacharjee is the Senior Research Fellow (SRF) in the Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India awarded by Indian Council of Medical Research (ICMR), New Delhi, India. His areas of expertise are medicinal chemistry, nanotechnology and cancer chemotherapy. His research work deals with the evaluation of nano-selenium as an adjuvant in cancer chemotherapy in order to reduce the toxic manifestations of chemotherapy and simultaneously to enhance therapeutic efficacy of conventional antineoplastic agents.

Subhadip Hajra is the Young Scientist in the Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India awarded by Department of Science and Technology (DST), New Delhi, India. His areas of expertise are microbiology, phytology, pharmacology and cancer biology. He has 16 publications and several book chapters. His research work includes phytochemistry, pharmacological screening of natural products, redox regulation in pathological conditions, and genotoxicology. He currently aims to establish natural product-based cost-effective chemotherapeutic regimen.

Amalesh Samanta is the Professor in the Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata. His areas of expertise are formulation designing, antimicrobial and pharmacological screening of phytoconstituents, polymer science and prebiotic evaluation from natural polysaccharides as an immune booster and anticancer agent. He has 78 publications in national and international journals of repute. His research work deals with the development of natural materials to address modern day diseases like colon cancer, food poisoning and enteric diseases.

Sudin Bhattacharya is the Head, Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. His areas of expertise are medicinal chemistry, anticancer drug development, drug designing, pharmacology, toxicology and cancer biology. He has 76 publications including book chapters. His research work includes synthesis and evaluation of antioxidative as well as cancer chemopreventive properties of small molecules and reduction of the toxic manifestation imparted by different cancer chemotherapeutic drugs by organic small molecules, nano-selenium and complementary alternative medicines.

Additional information

Funding

Abhishek Basu and Arin Bhattacharjee gratefully acknowledge Indian Council of Medical Research (ICMR) for Senior Research Fellowship (no. 3/2/2/58/2011/NCD-III and no. 45/36/2008/PHA-BMS). Subhadip Hajra also gratefully acknowledges Science and Engineering Research Board (SERB), Department of Science and Technology (DST) for Start-Up Research Grant (no. SB/YS/LS-121/2014).