Brief exposure to nanosized and bulk titanium dioxide forms induces subtle changes in human D384 astrocytes. (8th July 2016)

• Record Type: Journal Article
• Authors: De Simone, Uliana; Lonati, Davide; Ronchi, Anna; Coccini, Teresa
• Is Part Of: Toxicology letters. Volume 254(2016)
• Page Start: 8
• Page End: 21
• Publication Date: 2016-07-08
• Subjects: CNS -- In vitro -- Nanotoxicity -- TiO2 -- Molecular mechanism -- Safety; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.05.006
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: TiO2 NPs caused subtle effects in human astrocytes D384 cells at not cytotoxic doses. Oxidative stress and apoptotic mechanisms occurred after low dose exposure to TiO2 NP. Comparatively, similar effects were observed when testing TiO2 bulk. Cellular checkpoint perturbations were associated with increasing intracellular Ti. Abstract: Although nanosized-titanium dioxide particles (TiO2 NPs)-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 TiO2 NPs 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 TiO2 NP 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 TiO2 NP 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 TiO2 NP 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.