Article

Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity.

Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7431, USA.
Environmental Science and Technology (Impact Factor: 5.26). 07/2006; 40(14):4346-52.
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.

1 Bookmark
 · 
222 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the last 30 years, the use of engineered nanoparticles (NPs) has progressively increased in many industrial and medical applications. In therapy, NPs may allow more effective cellular and subcellular targeting of drugs. In diagnostic applications, quantum dots are exploited for their optical characteristics, while superparamagnetic iron oxides NPs are used in magnetic resonance imaging. NPs are used in semiconductors, packaging, textiles, solar cells, batteries and plastic materials. Despite the great progress in nanotechnologies, comparatively little is known to date on the effects that exposure to NPs may have on the human body, in general and specifically on the brain. NPs can enter the human body through skin, digestive tract, airways and blood and they may cross the blood-brain barrier to reach the central nervous system. In addition to the paucity of studies describing NP effects on brain function, some of them also suffer of insufficient NPs characterization, inadequate standardization of conditions and lack of contaminant evaluation, so that results from different studies can hardly be compared. It has been shown in vitro and in vivo in rodents that NPs can impair dopaminergic and serotoninergic systems. Changes of neuronal morphology and neuronal death were reported in mice treated with NPs. NPs can also affect the respiratory chain of mitochondria and Bax protein levels, thereby causing apoptosis. Changes in expression of genes involved in redox pathways in mouse brain regions were described. NPs can induce autophagy, and accumulate in lysosomes impairing their degradation capacity. Cytoskeleton and vesicle trafficking may also be affected. NPs treated animals showed neuroinflammation with microglia activation, which could induce neurodegeneration. Considering the available data, it is important to design adequate models and experimental systems to evaluate in a reliable and controlled fashion the effects of NPs on the brain, and generate data representative of effects on the human brain, thereby useful for developing robust and valid nanosafety standards.
    Progress in Neurobiology 05/2014; · 9.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and can be deposited in the hippocampus region; therefore, we determined the toxic effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated some events related to oxidative stress: 1) redox-signaling mechanisms by oxidation of 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA); 2) peroxidation of lipids by cis-parinaric acid; 3) antioxidant enzymes expression by PCR in real time; and 4) mitochondrial damage by MitoTracker Green FM staining and Rh123. TiO2 NPs induced a strong oxidative stress in both glial cell lines by mediating changes in the cellular redox state and lipid peroxidation associated to a rise in the expression of glutathione peroxidase (GPx), catalase and superoxide dismutase 2 (SOD2). TiO2 NPs also produced morphological changes, damage of mitochondria, and an increase of mitochondrial membrane potential, indicating toxicity. TiO2 NPs had a cytotoxic effect on glial cells; however, more in vitro and in vivo studies are required to ascertain that exposure to TiO2 NPs can cause brain injury and be hazardous to health.
    Free Radical Biology & Medicine 05/2014; · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aquatic toxicity of titanium dioxide nanoparticles (TiO2 NPs) to Daphnia magna was characterized using a completely stirred bioassay system intended to keep particles in suspension thereby maintaining a consistent exposure. The 48-h LC50 was 4.5 mg/L TiO2 NPs, whereas LC50 values for 7 and 14-days exposures were 2.7 and 1.9 mg/L, respectively. An exposure of 1.5 mg/L over a 21-days exposure resulted in significant reductions in fecundity. While reproduction was initially reduced in the 0.5 and 1.0 mg/L exposures, it recovered and was similar to the control by 21 days. For reproduction inhibition, NOEC was 1.0 mg/L. Exposure to 2.5 mg/L TiO2 NPs resulted in 40 % of the organisms failing to become gravid; all surviving organisms exposed to 5.0 mg/L failed to become gravid. The increased sensitivity was due to the refinement in the bioassay system that kept NP in suspension resulting in consistent exposure concentrations.
    Bulletin of Environmental Contamination and Toxicology 05/2014; · 1.11 Impact Factor

Full-text (2 Sources)

View
38 Downloads
Available from
Jun 10, 2014