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

doi:10.18071/isz.71.0035

Cited by 6 publications

(12 citation statements)

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“…Similarly, the more extensively investigated TiO 2 -nanoparticles also translocate to the brains of fish, where they can induce alterations in oxidative damage and cell death, neurotransmitter levels, locomotor behavior and spatial recognition memory [55][56][57][58]. In rodents, oral, intranasal or intratracheal exposure to TiO 2 -nanoparticles (size range 5-100 nm) resulted in oxidative stress and neuroinflammation [59,60], dysregulation of the glutamatergic signaling and alterations in neurotransmitter levels [59,61,62], changes in AChE activity [60,61], impaired motor function [63], reduction of long-term potentiation, and impairment of learning and memory [61,64]. Additional in vitro studies confirmed the ability of TiO 2 -nanoparticles to induce oxidative stress and neuroinflammation [65][66][67][68].…”

Section: Main Text Neurotoxicity Of Chemically Inert Metal(oxide) Nanoparticlesmentioning

confidence: 99%

The plastic brain: neurotoxicity of micro- and nanoplastics

2020

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Given the global abundance and environmental persistence, exposure of humans and (aquatic) animals to micro- and nanoplastics is unavoidable. Current evidence indicates that micro- and nanoplastics can be taken up by aquatic organism as well as by mammals. Upon uptake, micro- and nanoplastics can reach the brain, although there is limited information regarding the number of particles that reaches the brain and the potential neurotoxicity of these small plastic particles.Earlier studies indicated that metal and metal-oxide nanoparticles, such as gold (Au) and titanium dioxide (TiO2) nanoparticles, can also reach the brain to exert a range of neurotoxic effects. Given the similarities between these chemically inert metal(oxide) nanoparticles and plastic particles, this review aims to provide an overview of the reported neurotoxic effects of micro- and nanoplastics in different species and in vitro. The combined data, although fragmentary, indicate that exposure to micro- and nanoplastics can induce oxidative stress, potentially resulting in cellular damage and an increased vulnerability to develop neuronal disorders. Additionally, exposure to micro- and nanoplastics can result in inhibition of acetylcholinesterase activity and altered neurotransmitter levels, which both may contribute to the reported behavioral changes.Currently, a systematic comparison of the neurotoxic effects of different particle types, shapes, sizes at different exposure concentrations and durations is lacking, but urgently needed to further elucidate the neurotoxic hazard and risk of exposure to micro- and nanoplastics.

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Section: Main Text Neurotoxicity Of Chemically Inert Metal(oxide) Nanoparticlesmentioning

confidence: 99%

The plastic brain: neurotoxicity of micro- and nanoplastics

2020

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“…The in vivo doses applied here were in the same range as it has been found effective in previous works with spherical TiO 2 NPs. 30 , 49 Compared to the human exposure limit mostly referred to (0.3 mg/m 3 for nano-TiO 2 ; NIOSH), 51 our in vivo doses were about two orders of magnitude higher, but the time span of application (28 times over 6 weeks) was rather short. Details of this comparison were described in Ref.…”

Section: Discussionmentioning

confidence: 77%

“…70 In our previous studies, altered open field and grip strength test performance were detected in rats treated with spherical TiO 2 NPs. 49,71 In mice, deterioration of spatial memory, together with biochemical and electrophysiological signs of neuronal damage, have been reported. 18 In a state of energy shortage due to mitochondrial damage, spontaneous cortical activity is expected to become slower as it is known in mitochondriopathies.…”

Section: Discussionmentioning

confidence: 99%

“…48 Hence, SS EPs were also recorded using one series of stimuli with 2 and 10 Hz frequency beyond the standard 1 Hz. Based on the observed effects of nano-TiO 2 on motor behavior, 49 it was examined if the connection between the motor cortical area and the caudato-putamen was influenced by the treatment. The cortex was stimulated by applying the stimulus trains of 50 described above, at 1 Hz frequency, via a bipolar electrode.…”

Section: Investigation Of Central and Peripheral Electrophysiologicalmentioning

confidence: 99%

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<p>Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods</p>

Papp

Horváth

Igaz

et al. 2020

IJN

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Background Non-spherical titanium dioxide (TiO 2 ) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles. Materials and Methods Anatase form TiO 2 nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods. Results The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO 2 nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects. Conclusion Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO 2 nanoparticles.

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“…Both low and high doses increased latencies of somatosensory, auditory, and visual evoked potentials. Somatosensory latencies correlated with the concentration of titanium in cortex …”

Section: Adverse Outcome Pathwaymentioning

confidence: 99%

Neurotoxicology of Nanomaterials

Boyes

Thriel

2020

Chem. Res. Toxicol.

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The remarkable advances coming about through nanotechnology promise to revolutionize many aspects of modern life; however, these advances come with a responsibility for due diligence to ensure that they are not accompanied by adverse consequences for human health or the environment. Many novel nanomaterials (having at least one dimension <100 nm) could be highly mobile if released into the environment and are also very reactive, which has raised concerns for potential adverse impacts including, among others, the potential for neurotoxicity. Several lines of evidence led to concerns for neurotoxicity, but perhaps none more than observations that inhaled nanoparticles impinging on the mucosal surface of the nasal epithelium could be internalized into olfactory receptor neurons and transported by axoplasmic transport into the olfactory bulbs without crossing the blood−brain barrier. From the olfactory bulb, there is concern that nanomaterials may be transported deeper into the brain and affect other brain structures. Of course, people will not be exposed to only engineered nanomaterials, but rather such exposures will occur in a complex mixture of environmental materials, some of which are incidentally generated particles of a similar inhalable size range to engineered nanomaterials. To date, most experimental studies of potential neurotoxicity of nanomaterials have not considered the potential exposure sources and pathways that could lead to exposure, and most studies of nanomaterial exposure have not considered potential neurotoxicity. Here, we present a review of potential sources of exposures to nanoparticles, along with a review of the literature on potential neurotoxicity of nanomaterials. We employ the linked concepts of an aggregate exposure pathway (AEP) and an adverse outcome pathway (AOP) to organize and present the material. The AEP includes a sequence of key events progressing from material sources, release to environmental media, external exposure, internal exposure, and distribution to the target site. The AOP begins with toxicant at the target site causing a molecular initiating event and, like the AEP, progress sequentially to actions at the level of the cell, organ, individual, and population. Reports of nanomaterial actions are described at every key event along the AEP and AOP, except for changes in exposed populations that have not yet been observed. At this last stage, however, there is ample evidence of population level effects from exposure to ambient air particles that may act similarly to engineered nanomaterials. The data give an overall impression that current exposure levels may be considerably lower than those reported experimentally to be neurotoxic. This impression, however, is tempered by the absence of long-term exposure studies with realistic routes and levels of exposure to address concerns for chronic accumulation of materials or damage. Further, missing across the board are "key event relationships", which are quantitative expressions linking the key events of either the AEP or ...

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

Abstract: 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.

Cited by 6 publications

References 15 publications

The plastic brain: neurotoxicity of micro- and nanoplastics

The plastic brain: neurotoxicity of micro- and nanoplastics

<p>Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods</p>

Neurotoxicology of Nanomaterials

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