Article

Titanium Dioxide (P25) Produces Reactive Oxygen Species in Immortalized Brain Microglia (BV2): Implications for Nanoparticle Neurotoxicity

Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, North Carolina, United States
Environmental Science and Technology (Impact Factor: 5.33). 07/2006; 40(14):4346-52. DOI: 10.1021/es060589n
Source: PubMed

ABSTRACT

Concerns with the environmental and health risk of widely distributed, commonly used nanoparticles are increasing. Nanosize titanium dioxide (TiO2) is used in air and water remediation and in numerous products designed for direct human use and consumption. Its effectiveness in deactivating pollutants and killing microorganisms relates to photoactivation and the resulting free radical activity. This property, coupled with its multiple potential exposure routes, indicates that nanosize TiO2 could pose a risk to biological targets that are sensitive to oxidative stress damage (e.g., brain). In this study, brain microglia (BV2) were exposed to a physicochemically characterized (i.e., dispersion stability, particle size distribution, and zeta potential) nanomaterial, Degussa P25, and cellular expressions of reactive oxygen species were measured with fluorescent probes. P25's zeta potentials, measured in cell culture media and physiological buffer were -11.6 +/- 1.2 mV and -9.25 +/- 0.73 mV, respectively. P25 aggregation was rapid in both media and buffer with the hydrodynamic diameter of stable P25 aggregates ranging from 826 nm to 2368 nm depending on the concentration. The biological response of BV2 microglia to noncytotoxic (2.5-120 ppm) concentrations of P25 was a rapid (<5 min) and sustained (120 min) release of reactive oxygen species. The time course of this release suggested that P25 not only stimulated the immediate "oxidative burst" response in microglia but also interfered with mitochondrial energy production. Transmission electron microscopy indicated that small groups of nanosized particles and micron-sized aggregates were engulfed bythe microglia and sequestered as intracytoplasmic aggregates after 6 and 18 h exposure to P25 (2.5 ppm). Cell viability was maintained at all test concentrations (2.5-120 ppm) over the 18 h exposure period. These data indicate that mouse microglia respond to Degussa P25 with cellular and morphological expressions of free radical formation.

Download full-text

Full-text

Available from: Robert D Tilton
  • Source
    • "Hydrothermal synthesis would have greater commercial viability if the nanoparticles could be synthesized more rapidly in the reaction vessels (Sohaebuddin et al. 2010; Thevenot et al. 2008). A common feature emerging from recent studies is that exposure of cells to TiO 2 nanoparticles increases the generation of reactive oxygen species (ROS) (Donaldson et al. 2003; Olmedo et al. 2005; Long et al. 2006, 2007). However, whether or not the increase of ROS is truly responsible for the cytotoxic effects of nanoparticles is still unknown. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mosquito vectors (Diptera: Culicidae) are responsible for transmission of serious diseases worldwide. Mosquito control is being enhanced in many areas, but there are significant challenges, including increasing resistance to insecticides and lack of alternative, cost-effective, and eco-friendly products. To deal with these crucial issues, recent emphasis has been placed on plant materials with mosquitocidal properties. Furthermore, cancers figure among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Nanotechnology is a promising field of research and is expected to give major innovation impulses in a variety of industrial sectors. In this study, we synthesized titanium dioxide (TiO2) nanoparticles using the hydrothermal method. Nanoparticles were subjected to different analysis including UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential, and energy-dispersive spectrometric (EDX). The synthesized TiO2 nanoparticles exhibited dose-dependent cytotoxicity against human breast cancer cells (MCF-7) and normal breast epithelial cells (HBL-100). After 24-h incubation, the inhibitory concentrations (IC50) were found to be 60 and 80 μg/mL on MCF-7 and normal HBL-100 cells, respectively. Induction of apoptosis was evidenced by Acridine Orange (AO)/ethidium bromide (EtBr) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. In larvicidal and pupicidal experiments conducted against the primary dengue mosquito Aedes aegypti, LC50 values of nanoparticles were 4.02 ppm (larva I), 4.962 ppm (larva II), 5.671 ppm (larva III), 6.485 ppm (larva IV), and 7.527 ppm (pupa). Overall, our results suggested that TiO2 nanoparticles may be considered as a safe tool to build newer and safer mosquitocides and chemotherapeutic agents with little systemic toxicity.
    Full-text · Article · Jan 2016 · Parasitology Research
  • Source
    • "Compared to titanium dioxide (TiO 2 ) NPs, ZnO NPs exert relatively strong toxic effects on human pulmonary epithelial cells, and the toxicities of both kinds of metal oxide NPs are controlled by their physicochemical characteristics (e.g., size and crystal phase) [3]. Regarding the underlying mechanism of toxicity, TiO 2 NPs promote the generation of intracellular reactive oxygen species (ROS) by modulating cell metabolism with light [4], whereas overproduction of ROS may damage the antioxidant mechanism in macrophages [5] and cause toxic effects in brain microglia or other cells [6] [7]. Similarly, ZnO NPs may cause oxidative stress in macrophages and "
    [Show abstract] [Hide abstract]
    ABSTRACT: Owing to the wide use of novel nanoparticles (NPs) such as zinc oxide (ZnO) in all aspects of life, toxicological research on ZnO NPs is receiving increasing attention in these days. In this study, the toxicity of ZnO NPs in a human pulmonary adenocarcinoma cell line LTEP-a-2 was tested in vitro. Log-phase cells were exposed to different levels of ZnO NPs for hours, followed by colorimetric cell viability assay using tetrazolium salt and cell survival rate assay using trypan blue dye. Cell morphological changes were observed by Giemsa staining and light microscopy. Apoptosis was detected by using fluorescence microscopy and caspase-3 activity assay. Both intracellular reactive oxygen species (ROS) and reduced glutathione (GSH) were examined by a microplate-reader method. Results showed that ZnO NPs (≥0.01 μg/mL) significantly inhibited proliferation ( P < 0.05 ) and induced substantial apoptosis in LTEP-a-2 cells after 4 h of exposure. The intracellular ROS level rose up to 30–40% corresponding to significant depletion (approximately 70–80%) in GSH content in LTEP-a-2 cells ( P < 0.05 ), suggesting that ZnO NPs induced apoptosis mainly through increased ROS production. This study elucidates the toxicological mechanism of ZnO NPs in human pulmonary adenocarcinoma cells and provides reference data for application of nanomaterials in the environment.
    Full-text · Article · Sep 2015
  • Source
    • "c o m / l o c a t e / c e j Although nano TiO 2 is thought to be nontoxic, its release to aquatic environments could still pose serious threat to human beings and ecosystems. This is because TiO 2 NPs are capable of generating very oxidative free radicals when they are exposed to sun light [16] [17]. Therefore, immobilizing TiO 2 NPs onto environment benign supporting materials orders of magnitude bigger has been tried as a possible solution to using these small particles for environmental remediation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A variety of nano-TiO2/cellulose composite fibers (TiO2/CF) were synthesized via both in situ growing rutile TiO2 nanocrystals and electrostatic self-assembly of commercial nano rutile TiO2 particles onto cellulose fibers. These fibers were then processed into fibrous membrane beds by wet-laid technique. Dynamic adsorption of lead (Pb2+) was subsequently carried out by pumping the feed solution through the bed in a single-pass flow mode. The influence of various parameters including flow rate, bed height and bed stacking pattern on bed breakthrough behavior was investigated. It was found that the in situ-TiO2/CF bed outperformed others; its loading capacity of Pb2+ was 13 times that of pure CF bed, and 9 times that of the self-assembled TiO2/cellulose bed prior to 10% breakthrough. The dynamic adsorption behavior of the in situ-TiO2/CF bed was better predicted by Dose-Response model among other models tested. The bed was also selective for Pb2+ over Ca2+, and was readily regenerable when eluted with 0.1M HCl solution for repeated use. The outstanding performance of the in situ-TiO2/CF bed was a result of larger fiber adsorption capacity and faster adsorption kinetics compared with the other beds having similar geometric bed structure.
    Full-text · Article · Aug 2015
Show more