Web Release Date: June 7,
Titanium Dioxide (P25) Produces
Reactive Oxygen Species in
Immortalized Brain Microglia (BV2):
Implications for Nanoparticle
Neurotoxicity
and
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7431, Department of Civil and Environmental Engineering, Department of Chemical Engineering, and Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711
Received for review March 13, 2006
Revised manuscript received April 28, 2006
Accepted May 3, 2006
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 by the 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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