Titanium dioxide nanoparticle-induced oxidative stress triggers DNA damage and hepatic injury in mice

Nanomedicine (Lond). 2014 Jul;9(9):1423-34. doi: 10.2217/nnm.13.100. Epub 2013 Dec 24.

Abstract

Background: The use of metal oxide nanoparticles (titanium dioxide) in consumer and industrial products improves their quality but also underscores the possible adverse effects to human and environmental health.

Materials & methods: Mice were exposed orally for 14 consecutive days and analyzed for alteration in different hepatic enzymes, histopathological changes, oxidative stress, DNA damage, tumor suppressor and proapoptotic protein expression in liver cells.

Results: We observed a significant alteration in the level of hepatic enzymes and liver histopathology at a dose of 100 mg/kg body weight. Significant oxidative DNA damage was observed in liver cells, which could be attributed to oxidative stress. In addition, the increased expression of p53, BAX, caspase-3 and -9 proteins and decreased expression of antiapoptotic protein Bcl-2, suggest activation of the intrinsic pathway of apoptosis.

Conclusion: High accumulation of titanium dioxide nanoparticles in the liver tissue would cause DNA damage and apoptosis through the intrinsic pathway.

Keywords: DNA damage; apoptosis; fpg Comet assay; histopathological changes; liver; mouse; oxidative stress; titanium dioxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • DNA Damage*
  • Heat-Shock Proteins / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Liver / drug effects*
  • Liver / injuries*
  • Liver / metabolism
  • Male
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / toxicity*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Micronucleus Tests
  • Nanomedicine
  • Oxidative Stress / drug effects
  • Titanium / administration & dosage
  • Titanium / toxicity*

Substances

  • Heat-Shock Proteins
  • titanium dioxide
  • Titanium