Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells

Free Radic Biol Med. 2014 Aug:73:84-94. doi: 10.1016/j.freeradbiomed.2014.04.026. Epub 2014 May 10.


Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical, and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and can be deposited in the hippocampus region; therefore, we determined the toxic effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated some events related to oxidative stress: (1) redox-signaling mechanisms by oxidation of 2',7'-dichlorodihydrofluorescein diacetate; (2) peroxidation of lipids by cis-parinaric acid; (3) antioxidant enzyme expression by PCR in real time; and (4) mitochondrial damage by MitoTracker Green FM staining and Rh123. TiO2 NPs induced a strong oxidative stress in both glial cell lines by mediating changes in the cellular redox state and lipid peroxidation associated with a rise in the expression of glutathione peroxidase, catalase, and superoxide dismutase 2. TiO2 NPs also produced morphological changes, damage of mitochondria, and an increase in mitochondrial membrane potential, indicating toxicity. TiO2 NPs had a cytotoxic effect on glial cells; however, more in vitro and in vivo studies are required to ascertain that exposure to TiO2 NPs can cause brain injury and be hazardous to health.

Keywords: Free radicals; Glial cells; Lipoperoxidation; Mitochondrial damage; Nanoparticles; Oxidative stress; ROS; Titanium dioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Injuries / chemically induced*
  • Catalase / biosynthesis
  • Catalase / genetics
  • Cell Line, Tumor
  • Fatty Acids, Unsaturated / metabolism
  • Fluoresceins / metabolism
  • Glutathione Peroxidase / biosynthesis
  • Glutathione Peroxidase / genetics
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Metal Nanoparticles / toxicity*
  • Mitochondria / drug effects*
  • Neuroglia / cytology
  • Neuroglia / pathology
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • RNA, Messenger / biosynthesis
  • Superoxide Dismutase / biosynthesis
  • Superoxide Dismutase / genetics
  • Titanium / toxicity*


  • Fatty Acids, Unsaturated
  • Fluoresceins
  • RNA, Messenger
  • dihydrofluorescein
  • titanium dioxide
  • Titanium
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • parinaric acid