Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats

Asian Pac J Cancer Prev. 2015;16(16):6877-82. doi: 10.7314/apjcp.2015.16.16.6877.

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.

Materials and 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.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antineoplastic Agents / toxicity
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Catalase / blood
  • Cisplatin / toxicity
  • Creatinine / blood
  • Drug Therapy, Combination
  • Female
  • Glutathione / blood
  • Glutathione Peroxidase / blood
  • Malondialdehyde / blood
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Selenium / therapeutic use*
  • Urea / blood
  • Vitamin E / administration & dosage*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Vitamin E
  • Malondialdehyde
  • Urea
  • Creatinine
  • Catalase
  • Glutathione Peroxidase
  • Glutathione
  • Selenium
  • Cisplatin