Differences in the toxicity of cerium dioxide nanomaterials after inhalation can be explained by lung deposition, animal species and nanoforms

Dekkers, Susan; Ma‐Hock, Lan; Lynch, Iseult; Russ, Mike; Miller, Mark R.; Schins, Roel P. F.; Keller, Jana; Römer, Isabella; Küttler, Karin; Strauss, Volker; Jong, Wim H. de; Landsiedel, Robert; Cassee, Flemming R.

doi:10.1080/08958378.2018.1516834

Cited by 22 publications

(12 citation statements)

References 39 publications

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“…Detailed characteristics of NPs and their particle size distributions, mass and number exposure concentrations as well as lung deposited dose estimations for the inhalations are described in detail elsewhere ( Dekkers et al 2017 , 2018 ). Briefly, the different CeO 2 particles had a primary particle size of 4.7 ± 1.4 nm.…”

Section: Resultsmentioning

confidence: 99%

“…The aim of the current study was to evaluate the potential neurotoxic and neurodegenerative effects of CeO 2 NPs in mice following a four-week inhalation exposure and to assess the influence of redox activity by the concurrent evaluation of CeO 2 NPs with different Zr-doping grades. The investigations formed part of a large study conducted in to explore the (patho)physiological effects of NP exposure on multiple organ systems in various mouse models ( Dekkers et al 2017 , 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease

Wahle

Sofranko

Dekkers

et al. 2020

Neurochemistry International

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Increasing evidence from toxicological and epidemiological studies indicates that the brain is an important target for ambient (ultrafine) particles. Disturbance of redox-homeostasis and inflammation in the brain are proposed as possible mechanisms that can contribute to neurotoxic and neurodegenerative effects. Whether and how engineered nanoparticles (NPs) may cause neurotoxicity and promote neurodegenerative diseases such as Alzheimer's disease (AD) is largely unstudied. We have assessed the neurological effects of subacute inhalation exposures (4 mg/m 3 for 3 h/day, 5 days/week for 4 weeks) to cerium dioxide (CeO 2 ) NPs doped with different amounts of zirconium (Zr, 0%, 27% and 78%), to address the influence of particle redox-activity in the 5xFAD transgenic mouse model of AD. Four weeks post-exposure, effects on behaviour were evaluated and brain tissues were analysed for amyloid-β plaque formation and reactive microglia (Iba-1 staining). Behaviour was also evaluated in concurrently exposed non-transgenic C57BL/6J littermates, as well as in Western diet-fed apolipoprotein E-deficient (ApoE -/- ) mice as a model of vascular disease. Markers of inflammation and oxidative stress were evaluated in brain cortex. The brains of the NP-exposed 5xFAD mice revealed no accelerated amyloid-β plaque formation. No significant treatment-related behaviour impairments were observed in the healthy C57BL/6J mice. In the 5xFAD and ApoE -/- models, the NP inhalation exposures did not affect the alternation score in the X-maze indicating absence of spatial working memory deficits. However, following inhalation exposure to the 78% Zr-doped CeO 2 NPs changes in forced motor performance (string suspension) and exploratory motor activity (X-maze) were observed in ApoE -/- and 5xFAD mice, respectively. Exposure to the 78% doped NPs also caused increased cortical expression of glial fibrillary acidic protein (GFAP) in the C57BL/6J mice. No significant treatment-related changes neuroinflammation and oxidative stress were observed in the 5xFAD and ApoE -/- mice. Our study findings reveal that subacute inhalation exposure to CeO 2 NPs does not accelerate the AD-like phenotype of the 5xFAD model. Further investigation is warranted to unravel whether the redox-activity dependent effects on motor activity as observed in the mouse models of AD and vascular disease result from specific neurotoxic effects of these NPs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease

Wahle

Sofranko

Dekkers

et al. 2020

Neurochemistry International

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“…The toxicity of CeO 2 NPs remains controversial, because conflicting results have been reported in the scientific community, with both pro-oxidant and anti-oxidant effects in tissues. This variability depends mostly on the cell type, but also on the physical and chemical characteristics of nanoceria, like the aggregation state, the shape (nanocubes vs. nanorods), surface modifications and the oxidative status of the cerium (Ce) [ 29 , 30 ]. Altogether, these properties modulate the nanoceria’s behavior in different environments and thus its distribution, elimination and toxicity, at both the cellular level and in the body.…”

Section: Introductionmentioning

confidence: 99%

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta

et al. 2020

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The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO2 NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO2 NPs could contribute to a better understanding of NPs’ effect on the development and functions of the placenta and pregnancy outcome. We used primary villous cytotrophoblasts purified from term human placenta, with a wide range of CeO2 NPs concentrations (0.1–101 μg/cm2) and exposure time (24–72 h), to assess trophoblast uptake, toxicity and impact on trophoblast differentiation and endocrine function. We have shown the capacity of both cytotrophoblasts and syncytiotrophoblasts to internalize CeO2 NPs. CeO2 NPs affected trophoblast metabolic activity in a dose and time dependency, induced caspase activation and a LDH release in the absence of oxidative stress. CeO2 NPs decreased the fusion capacity of cytotrophoblasts to form a syncytiotrophoblast and disturbed secretion of the pregnancy hormones hCG, hPL, PlGF, P4 and E2, in accordance with NPs concentration. This is the first study on the impact of CeO2 NPs using human primary trophoblasts that decrypts their toxicity and impact on placental formation and functions.

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“…[19][20][21][22][23] In contrast to research about the antioxidant activity of CeNPs, inhalable CeNPs have been detected in ambient air and concerns have been raised about their potential adverse health effect. 24,25 Besides this, additional studies suggested that CeNPs can induce oxidative stress, inammatory signaling response, and cell death upon generating ROS (processes ④-⑥ in Scheme 1) or ROS-messengers. [26][27][28][29][30] Given the controversies about the benecial and toxic effects of CeNPs, it is necessary to distinguish the anti-and prooxidant activities of CeNPs under physiologically relevant conditions.…”

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confidence: 99%

Antioxidant activity of cerium dioxide nanoparticles and nanorods in scavenging hydroxyl radicals

et al. 2019

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Differences in the toxicity of cerium dioxide nanomaterials after inhalation can be explained by lung deposition, animal species and nanoforms

Cited by 22 publications

References 39 publications

Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease

Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta

Antioxidant activity of cerium dioxide nanoparticles and nanorods in scavenging hydroxyl radicals

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