The Protective Effect of Naringenin on Oxaliplatin-Induced Genotoxicity in Mice

Chem Pharm Bull (Tokyo). 2019 May 1;67(5):433-438. doi: 10.1248/cpb.c18-00809. Epub 2019 Feb 20.

Abstract

Oxaliplatin is a third generation platinum based anti-cancer drug used against various human malignancies but displays genotoxic properties against normal cells. Naringenin is a naturally occurring bioflavonoid that possesses anti-oxidant properties and has protective effects against DNA damage. The aim of this study is to examine the protective effects of naringenin on oxaliplatin-induced DNA damage in mice. A total of 50, male BALB/c mice were randomly divided equally into five groups. Oxaliplatin toxicity was induced by a single dose (7 mg/kg body weight (b.w.)) injection (intraperitoneally (i.p.)) of oxaliplatin. Naringenin was given orally for ten consecutive days at two doses, 20 mg/kg b.w. (dose I) and 40 mg/kg b.w. (dose II), to group I and group II, respectively. On the tenth day of the experiment, animals in groups III, IV, and V were given a single i.p. injection of oxaliplatin (7 mg/kg b.w.). All the animals were sacrificed 24 h after oxaliplatin treatment. The extent of genotoxicity was assessed by multiple genotoxicity assays (8-hydroxydeoxy-guanosine marker, comet, micronucleus and chromosomal aberration assays, oxidative stress-marker Glutathione evaluation) in order to determine diverse kinds of DNA damage. The results indicated that naringenin administration significantly reduced the DNA damage induced by oxaliplatin possibly due to its strong anti-oxidant properties. The results suggest that naringenin is a potential candidate for future development as a chemoprotective agent against chemotherapy associated complications.

Keywords: DNA damage; chemoprotective agent; genotoxicity; naringenin; oxaliplatin.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Chromosome Aberrations / drug effects
  • DNA Damage / drug effects*
  • Flavanones / administration & dosage
  • Flavanones / pharmacology*
  • Male
  • Mice, Inbred BALB C
  • Micronucleus Tests
  • Mutagens / adverse effects*
  • Oxaliplatin / adverse effects*
  • Oxidative Stress / drug effects

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Flavanones
  • Mutagens
  • Oxaliplatin
  • naringenin