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 24h exposure to TiO2NP concentrations (0.5-125μg/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 1.5μg/ml and further increased at the highest concentrations (≥31μg/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 24h, 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.
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, Salvatore Maugeri Foundation IRCCS, Scientific Institute of Pavia, Pavia, Italy.
authors.forename: Uliana
authors.initials: U
authors.lastname: De Simone
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, Salvatore Maugeri Foundation IRCCS, Scientific Institute of Pavia, Pavia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lonati
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, Salvatore Maugeri Foundation IRCCS, Scientific Institute of Pavia, Pavia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ronchi
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, Salvatore Maugeri Foundation IRCCS, Scientific Institute of Pavia, Pavia, Italy. Electronic address: teresa.coccini@fsm.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Coccini
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006801:Humans; D013058:Mass Spectrometry; D053768:Metal Nanoparticles; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: CNS; In vitro; Molecular mechanism; Nanotoxicity; Safety; TiO(2)