title: Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats.
abstract: BACKGROUND
  Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats.
  
  
  METHODS
  In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured.
  
  
  RESULTS
  The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05).
  
  
  CONCLUSIONS
  Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.
authors.affiliation: Department of Medical Oncology, Medical Faculty, Firat University, Turkey E-mail : asudeaksoy@hotmail.com.
authors.forename: Asude
authors.initials: A
authors.lastname: Aksoy
authors.forename: Aziz
authors.initials: A
authors.lastname: Karaoglu
authors.forename: Nusret
authors.initials: N
authors.lastname: Akpolat
authors.forename: Mustafa
authors.initials: M
authors.lastname: Naziroglu
authors.forename: Turkan
authors.initials: T
authors.lastname: Ozturk
authors.forename: Zuhal Karaca
authors.initials: ZK
authors.lastname: Karagoz
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002374:Catalase / Q000097:blood; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000627:therapeutic use*; D014508:Urea / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D014810:Vitamin E; D008315:Malondialdehyde; D014508:Urea; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D002945:Cisplatin