Brief exposure to nanosized and bulk titanium dioxide forms induces subtle changes in human D384 astrocytes

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Abstract

Although nanosized-titanium dioxide particles (TiO2NPs)-containing products are constantly placed on the market, little is known about their possible impact on human health, even regarding to CNS effects. In this study, mechanistic pathways, by which TiO2NPs induce cellular damage and death, have been investigated in human (astrocytes-like) D384 cells and comparatively weighed against the effects produced by the bulk counterpart. Cellular signals evaluated by multiple set of in vitro tests after 24 h exposure to TiO2NP concentrations (0.5-125 μg/ml) were: ROS production, p-p53, p53, p21, Bax, Bcl-2 and caspase 3. TiO2 cellular uptake was also estimated by both light microscopy and ICP-MS. ROS were generated starting at 1.5 μg/ml and further increased at the highest concentrations (≥31 μg/ml). At the same low concentration, an increased expression of p-p53, p53, p21, Bax, and activated caspase3 were also observed. Parallely, Bcl-2 decreased along with TiO2NP concentration increase. Similar alterations were observed when testing TiO2 bulk: cellular checkpoint perturbations were associated with rising intracellular Ti. The present data demonstrated that low TiO2NP concentrations were capable, after 24 h, to induce subtle cellular perturbation in D384 cells after a single cell treatment, supporting the evidence that both oxidative stress and apoptotic mechanisms may occur in this type of CNS cells.

Original languageEnglish
Pages (from-to)8-21
Number of pages14
JournalToxicology Letters
Volume254
DOIs
Publication statusPublished - Jul 8 2016

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Oxidative stress
Caspase 3
Astrocytes
Optical microscopy
Health
Testing
Microscopy
Oxidative Stress
Light
titanium dioxide

Keywords

  • CNS
  • In vitro
  • Molecular mechanism
  • Nanotoxicity
  • Safety
  • TiO

ASJC Scopus subject areas

  • Toxicology

Cite this

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title = "Brief exposure to nanosized and bulk titanium dioxide forms induces subtle changes in human D384 astrocytes",
abstract = "Although nanosized-titanium dioxide particles (TiO2NPs)-containing products are constantly placed on the market, little is known about their possible impact on human health, even regarding to CNS effects. In this study, mechanistic pathways, by which TiO2NPs induce cellular damage and death, have been investigated in human (astrocytes-like) D384 cells and comparatively weighed against the effects produced by the bulk counterpart. Cellular signals evaluated by multiple set of in vitro tests after 24 h exposure to TiO2NP concentrations (0.5-125 μg/ml) were: ROS production, p-p53, p53, p21, Bax, Bcl-2 and caspase 3. TiO2 cellular uptake was also estimated by both light microscopy and ICP-MS. ROS were generated starting at 1.5 μg/ml and further increased at the highest concentrations (≥31 μg/ml). At the same low concentration, an increased expression of p-p53, p53, p21, Bax, and activated caspase3 were also observed. Parallely, Bcl-2 decreased along with TiO2NP concentration increase. Similar alterations were observed when testing TiO2 bulk: cellular checkpoint perturbations were associated with rising intracellular Ti. The present data demonstrated that low TiO2NP concentrations were capable, after 24 h, to induce subtle cellular perturbation in D384 cells after a single cell treatment, supporting the evidence that both oxidative stress and apoptotic mechanisms may occur in this type of CNS cells.",
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author = "{De Simone}, Uliana and Davide Lonati and Anna Ronchi and Teresa Coccini",
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