Clinical Neuroscience

Functional neurotoxicity and tissue metal levels in rats exposed subacutely to titanium dioxide nanoparticles via the airways

HORVÁTH Tamara, VEZÉR Tünde, KOZMA Gábor, PAPP András

JANUARY 30, 2018

Clinical Neuroscience - 2018;71(01-02)


Introduction and aims - Nanoparticles of titanium dioxide are suspected neurotoxic agents and have numerous applications possibly resulting in human exposure by several ways including inhalation. In the present work, rats were exposed to spherical TiO2 nanoparticles of two different sizes by the intratracheal route. It was investigated how the neuro-functional alterations, detected by electrophysiological and behavioral methods, were related to the concentration of Ti in the tissue samples and what the influence of the size of the NPs was. Materials and methods - Rats (young adult Wistar males, 10/group) were exposed to TiO2 nanoparticles of ca. 10 and 100 nm diameter (suspension medium: neutral PBS with 1% hydroxyethyl cellulose) by intratracheal instillation in 5 and 18 mg/kg b.w. dose; 5 days per week for 6 weeks. Controls were instilled with saline, and vehicle controls, with the suspension medium. To see general toxicity, body weight was checked daily, and organ weights were measured at the end of experiment. Grip strength test, to assess motor function damage, was done before and after the 6-week treatment. Finally, the rats were anesthetized with urethane, spontaneous cortical activity and sensory evoked potentials were recorded, then the rats were dissected and tissue samples were taken for Ti level measurement. Results - Body weight gain indicated no general toxicity, and no significant change in the relative organ weights, except that of the lungs, was seen. However, change of time-to-fall in the grip strength test, and latency of cortical evoked po­tentials, were altered in the treated groups, indicating functional damage. Correlation of these alterations with the cortical Ti level was dissimilar for the two sizes of nanoparticles. Conclusion - The results provided further support to the functional neurotoxicity of TiO2 nanoparticles. The exact role of particle size, and the mechanisms involved, remain to be elucidated.



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Introduction and aims - Particles of titanium dioxide (TiO2) with typical size below 100 nm have gained a broad range of application by now, partly involving direct human exposure. Their known properties - high specific surface, mobility within the organism, induction of oxidative stress, release of inflammation mediators etc. - raise the possibility of nervous system damage but the available data regarding this are scarce and contradictory. Based on that, and the experiences with other metal oxide nanoparticles, the aim of the present study was to investigate certain general end nervous system toxic effects of TiO2 nanoparticles applied in the airways of rats. Materials and methods - Young adult Wistar rats (5 groups of 10 rats each) received, daily for 28 days, intratracheal instillations of titanium dioxide nanoparticles of ca. 10 nm diameter, suspended in 1% hydroxyethyl cellulose dissolved in phosphate-buffered saline, in the doses of 1, 3, and 10 mg/kg b. w. Vehicle controls received the suspension medium and there was also an untreated control group. During treatment, the rats’ body weight was measured, and their clinical state observed, daily. After the 28 days, spontaneous cortical activity, sensory evoked potentials and tail nerve action potential was recorded in urethane anesthesia, then the rats were dissected and tissue samples were taken for Ti level determination and biochemical measurements of some oxidative stress indicators. Results - The two higher doses reduced the rate of body weight gain significantly. Sensory evoked potentials and tail nerve action potential were significantly slowed, but the change in the spectrum of spontaneous cortical activity was not significant. Correlation of moderate strength was found between certain evoked potential parameters and brain Ti level and oxidative stress data. Conclusion - Our results underlined the possible neurotoxicity of TiO2 NPs but also the need for further investigations.