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


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.

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Available from: Robert D Tilton, Oct 10, 2015
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    • "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 "
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    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.
    09/2015; 2015(5617):423287. DOI:10.1155/2015/423287
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    • "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. "
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    • "These findings suggested that TiO 2 NPs-induced neuronal apoptosis may be associated with mitochondria-and endoplasmic reticulum-mediated signaling pathway. Long et al. (2006 and 2007) examined neurotoxicity of Aeroxide P25 NPs on mouse microglia BV2 cells, rat dopaminergic neurons (N27 cells) and primary cultures of rat striatum. Rapid, prolonged release of ROS was observed in BV2 cells upon Aeroxide P25 exposure, accompanied by increased caspase 3/7 activity and apoptotic loss of nuclear material. "
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    ABSTRACT: Titanium dioxide nanoparticles (TiO2 NPs) have found many practical applications in industry and daily life. A widespread application of TiO2 NPs rises the question about safety of their use in the context of potential occupational, environmental and intentional exposure of humans and biota. TiO2 NPs easily enter the body through inhalation, cross blood-brain barrier and accumulate in the brain, especially in the cortex and hippocampus. Toxicity of these NPs and the molecular mechanisms of their action have been studied extensively in recent years. Studies showed that TiO2 NPs exposure resulted in microglia activation, reactive oxygen species production, activation of signaling pathways involved in inflammation and cell death, both in vitro and in vivo. Consequently, such action led to neuroinflammation, further brain injury. A, spatial recognition memory and locomotor activity impairment has been also observed. Copyright © 2015. Published by Elsevier Ltd.
    Toxicology in Vitro 04/2015; 29(5). DOI:10.1016/j.tiv.2015.04.004 · 2.90 Impact Factor
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