Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure

Lora-Sophie Gerber; Dirk C A de Leijer; Andrea Rujas Arranz; Jonas M M L Lehmann; Meike E Verheul; Flemming R Cassee; Remco H S Westerink

doi:10.1016/j.scitotenv.2024.175469

Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure

Lora-Sophie Gerber, Dirk C A de Leijer, Andrea Rujas Arranz, Jonas M M L Lehmann, Meike E Verheul, Flemming R Cassee, Remco H S Westerink^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Exposure to traffic-related air pollution and ultrafine particles (<100 μm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e., solid UFP vs SVOC UFP, on neuronal function is unknown. We therefore studied effects on neuronal activity and viability in rat primary cortical cells exposed for up to 120 h to copper oxide particles (CuO) or UFP (solid and SVOC) emitted from a heavy-duty diesel engine fueled with petroleum diesel (A20; 20 % aromatics) or Hydrotreated Vegetable Oil-type fuel (A0; 0.1 % aromatics), or solid UFP emitted from a non-road Kubota engine fueled with A20. Moreover, effects of UFP and CuO upon simulated inhalation exposure were studied by exposing an lung model (Calu-3 and THP-1 cells) for 48 h and subsequently exposing the cortical cells to the medium collected from the basal compartment of the lung model. Additionally, cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress were studied in the lung model after 48 h exposure to UFP and CuO. Compared to control, direct exposure to CuO and SVOC UFP decreased neuronal activity, which was partly associated with cytotoxicity. Effects on neuronal activity upon direct exposure to solid UFP were limited. A20-derived UFP (solid and SVOC) were more potent in altering neuronal function and viability than A0 counterparts. Effects on neuronal activity from simulated inhalation exposure were minor compared to direct exposures. In the lung model, CuO and A20-derived UFP increased cytokine release compared to control, whereas CuO and SVOC A20 altered gene expression indicative for oxidative stress. Our data indicate that SVOC UFP exhibit higher (neuro)toxic potency for altering neuronal activity in rat primary cortical cells than the solid fraction. Moreover, our data suggest that reducing the aromatic content in fuel decreases the (neuro)toxic potency of emitted UFP.

Original language	English
Article number	175469
Journal	Science of the Total Environment
Volume	951
Early online date	15 Aug 2024
DOIs	https://doi.org/10.1016/j.scitotenv.2024.175469
Publication status	Published - 15 Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

We gratefully acknowledge Pasi Jalava from the University of Eastern Finland and Pa<spacing diaeresis>ivi <spacing diaeresis> ivi Aakko-Saksa from VTT Technical Research Centre (Finland) for generating and providing the ultrafine particle samples. Furthermore, we thank Evert Duistermaat from the National Institute for Public Health and the Environment (RIVM) for his great technical support and Jolanda Vermeulen and Eric Gremmer from the National Institute for Public Health and the Environment (RIVM) for their help with cell culturing THP-1 and Calu-3 cells, and the members of the Neurotoxicology Research Group (Utrecht University) for valuable discussions. This work has been funded by the European Union's Horizon2020 research and innovation programme under grant agreement No 814978 (TUBE) , the National Institute for Public Health and the Environment (RIVM, The Netherlands) , and the Faculty of Veterinary Medicine (Utrecht University, The Netherlands) . The authors declare they have no competing financial interests.r 2020 research and innovation programme under grant agreement No 814978 (TUBE) , the National Institute for Public Health and the Envi-ronment (RIVM, The Netherlands) , and the Faculty of Veterinary Med-icine (Utrecht University, The Netherlands) . The authors declare they have no competing financial interests.

Funders	Funder number
Itä-Suomen Yliopisto
Faculty of Veterinary Medicine, Kasetsart University
Päivi Aakko-Saksa
National Institute for Public Health and the Environment
Universiteit Utrecht
Rijksinstituut voor Volksgezondheid en Milieu
VTT Technical Research Centre
Horizon 2020	814978

Keywords

Air pollution
Diesel engine emission
Inhalation exposure
Microelectrode array (MEA) recordings
Neurotoxic hazard characterization
Semi-volatile organic compounds

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10.1016/j.scitotenv.2024.175469Licence: CC BY

1-s2.0-S0048969724056195-mainFinal published version, 15.9 MBLicence: CC BY

Cite this

Gerber, L.-S., de Leijer, D. C. A., Arranz, A. R., Lehmann, J. M. M. L., Verheul, M. E., Cassee, F. R., & Westerink, R. H. S. (2024). Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure. Science of the Total Environment, 951, Article 175469. https://doi.org/10.1016/j.scitotenv.2024.175469

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abstract = "Exposure to traffic-related air pollution and ultrafine particles (<100 μm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e., solid UFP vs SVOC UFP, on neuronal function is unknown. We therefore studied effects on neuronal activity and viability in rat primary cortical cells exposed for up to 120 h to copper oxide particles (CuO) or UFP (solid and SVOC) emitted from a heavy-duty diesel engine fueled with petroleum diesel (A20; 20 \% aromatics) or Hydrotreated Vegetable Oil-type fuel (A0; 0.1 \% aromatics), or solid UFP emitted from a non-road Kubota engine fueled with A20. Moreover, effects of UFP and CuO upon simulated inhalation exposure were studied by exposing an lung model (Calu-3 and THP-1 cells) for 48 h and subsequently exposing the cortical cells to the medium collected from the basal compartment of the lung model. Additionally, cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress were studied in the lung model after 48 h exposure to UFP and CuO. Compared to control, direct exposure to CuO and SVOC UFP decreased neuronal activity, which was partly associated with cytotoxicity. Effects on neuronal activity upon direct exposure to solid UFP were limited. A20-derived UFP (solid and SVOC) were more potent in altering neuronal function and viability than A0 counterparts. Effects on neuronal activity from simulated inhalation exposure were minor compared to direct exposures. In the lung model, CuO and A20-derived UFP increased cytokine release compared to control, whereas CuO and SVOC A20 altered gene expression indicative for oxidative stress. Our data indicate that SVOC UFP exhibit higher (neuro)toxic potency for altering neuronal activity in rat primary cortical cells than the solid fraction. Moreover, our data suggest that reducing the aromatic content in fuel decreases the (neuro)toxic potency of emitted UFP.",

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doi = "10.1016/j.scitotenv.2024.175469",

language = "English",

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Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure. / Gerber, Lora-Sophie; de Leijer, Dirk C A; Arranz, Andrea Rujas et al.
In: Science of the Total Environment, Vol. 951, 175469, 15.11.2024.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure

AU - Gerber, Lora-Sophie

AU - de Leijer, Dirk C A

AU - Arranz, Andrea Rujas

AU - Lehmann, Jonas M M L

AU - Verheul, Meike E

AU - Cassee, Flemming R

AU - Westerink, Remco H S

PY - 2024/11/15

Y1 - 2024/11/15

N2 - Exposure to traffic-related air pollution and ultrafine particles (<100 μm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e., solid UFP vs SVOC UFP, on neuronal function is unknown. We therefore studied effects on neuronal activity and viability in rat primary cortical cells exposed for up to 120 h to copper oxide particles (CuO) or UFP (solid and SVOC) emitted from a heavy-duty diesel engine fueled with petroleum diesel (A20; 20 % aromatics) or Hydrotreated Vegetable Oil-type fuel (A0; 0.1 % aromatics), or solid UFP emitted from a non-road Kubota engine fueled with A20. Moreover, effects of UFP and CuO upon simulated inhalation exposure were studied by exposing an lung model (Calu-3 and THP-1 cells) for 48 h and subsequently exposing the cortical cells to the medium collected from the basal compartment of the lung model. Additionally, cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress were studied in the lung model after 48 h exposure to UFP and CuO. Compared to control, direct exposure to CuO and SVOC UFP decreased neuronal activity, which was partly associated with cytotoxicity. Effects on neuronal activity upon direct exposure to solid UFP were limited. A20-derived UFP (solid and SVOC) were more potent in altering neuronal function and viability than A0 counterparts. Effects on neuronal activity from simulated inhalation exposure were minor compared to direct exposures. In the lung model, CuO and A20-derived UFP increased cytokine release compared to control, whereas CuO and SVOC A20 altered gene expression indicative for oxidative stress. Our data indicate that SVOC UFP exhibit higher (neuro)toxic potency for altering neuronal activity in rat primary cortical cells than the solid fraction. Moreover, our data suggest that reducing the aromatic content in fuel decreases the (neuro)toxic potency of emitted UFP.

AB - Exposure to traffic-related air pollution and ultrafine particles (<100 μm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e., solid UFP vs SVOC UFP, on neuronal function is unknown. We therefore studied effects on neuronal activity and viability in rat primary cortical cells exposed for up to 120 h to copper oxide particles (CuO) or UFP (solid and SVOC) emitted from a heavy-duty diesel engine fueled with petroleum diesel (A20; 20 % aromatics) or Hydrotreated Vegetable Oil-type fuel (A0; 0.1 % aromatics), or solid UFP emitted from a non-road Kubota engine fueled with A20. Moreover, effects of UFP and CuO upon simulated inhalation exposure were studied by exposing an lung model (Calu-3 and THP-1 cells) for 48 h and subsequently exposing the cortical cells to the medium collected from the basal compartment of the lung model. Additionally, cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress were studied in the lung model after 48 h exposure to UFP and CuO. Compared to control, direct exposure to CuO and SVOC UFP decreased neuronal activity, which was partly associated with cytotoxicity. Effects on neuronal activity upon direct exposure to solid UFP were limited. A20-derived UFP (solid and SVOC) were more potent in altering neuronal function and viability than A0 counterparts. Effects on neuronal activity from simulated inhalation exposure were minor compared to direct exposures. In the lung model, CuO and A20-derived UFP increased cytokine release compared to control, whereas CuO and SVOC A20 altered gene expression indicative for oxidative stress. Our data indicate that SVOC UFP exhibit higher (neuro)toxic potency for altering neuronal activity in rat primary cortical cells than the solid fraction. Moreover, our data suggest that reducing the aromatic content in fuel decreases the (neuro)toxic potency of emitted UFP.

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KW - Diesel engine emission

KW - Inhalation exposure

KW - Microelectrode array (MEA) recordings

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Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure

Abstract

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Keywords

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