Internalization of Titanium Dioxide Nanoparticles Is Cytotoxic for H9c2 Rat Cardiomyoblasts

Molecules. 2018 Aug 6;23(8):1955. doi: 10.3390/molecules23081955.


Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in industry and daily life. TiO₂ NPs can penetrate into the body, translocate from the lungs into the circulation and come into contact with cardiac cells. In this work, we evaluated the toxicity of TiO₂ NPs on H9c2 rat cardiomyoblasts. Internalization of TiO₂ NPs and their effect on cell proliferation, viability, oxidative stress and cell death were assessed, as well as cell cycle alterations. Cellular uptake of TiO₂ NPs reduced metabolic activity and cell proliferation and increased oxidative stress by 19-fold measured as H₂DCFDA oxidation. TiO₂ NPs disrupted the plasmatic membrane integrity and decreased the mitochondrial membrane potential. These cytotoxic effects were related with changes in the distribution of cell cycle phases resulting in necrotic death and autophagy. These findings suggest that TiO₂ NPs exposure represents a potential health risk, particularly in the development of cardiovascular diseases via oxidative stress and cell death.

Keywords: autophagy; cardiomyoblasts; internalization; necrosis; oxidative stress; titanium dioxide nanoparticles.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism*
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity*
  • Oxidative Stress / drug effects
  • Rats
  • Titanium / chemistry*
  • Titanium / toxicity*


  • titanium dioxide
  • Titanium