title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Basu
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India.
authors.forename: Arin
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Hajra
authors.affiliation: b Division of Microbiology, Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India.
authors.forename: Amalesh
authors.initials: A
authors.lastname: Samanta
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India.
authors.forename: Sudin
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D014638:Vanadates / Q000008:administration & dosage / Q000627:therapeutic use*; D017968:Vanadium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D017968:Vanadium Compounds; C075743:oxovanadium IV; D014638:Vanadates; D002945:Cisplatin
keywords: Nrf2/ARE pathway; Vanadium; antioxidant enzymes; apoptosis; atomic absorption spectroscopy; kidney damage; reactive oxygen species