Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats

J Biochem Mol Toxicol. 2013 Aug;27(8):398-405. doi: 10.1002/jbt.21501. Epub 2013 May 28.

Abstract

The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen.

Keywords: 8-hydroxy-2'-deoxyguanosine; benfotiamine; cisplatin; nitric oxide; paraoxonase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Aryldialkylphosphatase / metabolism
  • Catalase / metabolism
  • Cisplatin / administration & dosage*
  • Cisplatin / toxicity
  • DNA Damage / drug effects*
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Kidney / injuries
  • Malondialdehyde
  • Oxidative Stress / drug effects
  • Protective Agents / administration & dosage*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Thiamine / administration & dosage
  • Thiamine / analogs & derivatives*

Substances

  • Antioxidants
  • Protective Agents
  • Reactive Oxygen Species
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Aryldialkylphosphatase
  • Cisplatin
  • Thiamine
  • benphothiamine