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Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions

BACKGROUND: Recently, much progress has been made to develop more physiologic in vitro models of the respiratory system and improve in vitro simulation of particle exposure through inhalation. Nevertheless, the field of nanotoxicology still suffers from a lack of relevant in vitro models and exposur...

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Autores principales: Loret, Thomas, Peyret, Emmanuel, Dubreuil, Marielle, Aguerre-Chariol, Olivier, Bressot, Christophe, le Bihan, Olivier, Amodeo, Tanguy, Trouiller, Bénédicte, Braun, Anne, Egles, Christophe, Lacroix, Ghislaine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137211/
https://www.ncbi.nlm.nih.gov/pubmed/27919268
http://dx.doi.org/10.1186/s12989-016-0171-3
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author Loret, Thomas
Peyret, Emmanuel
Dubreuil, Marielle
Aguerre-Chariol, Olivier
Bressot, Christophe
le Bihan, Olivier
Amodeo, Tanguy
Trouiller, Bénédicte
Braun, Anne
Egles, Christophe
Lacroix, Ghislaine
author_facet Loret, Thomas
Peyret, Emmanuel
Dubreuil, Marielle
Aguerre-Chariol, Olivier
Bressot, Christophe
le Bihan, Olivier
Amodeo, Tanguy
Trouiller, Bénédicte
Braun, Anne
Egles, Christophe
Lacroix, Ghislaine
author_sort Loret, Thomas
collection PubMed
description BACKGROUND: Recently, much progress has been made to develop more physiologic in vitro models of the respiratory system and improve in vitro simulation of particle exposure through inhalation. Nevertheless, the field of nanotoxicology still suffers from a lack of relevant in vitro models and exposure methods to predict accurately the effects observed in vivo, especially after respiratory exposure. In this context, the aim of our study was to evaluate if exposing pulmonary cells at the air-liquid interface to aerosols of inhalable and poorly soluble nanomaterials generates different toxicity patterns and/or biological activation levels compared to classic submerged exposures to suspensions. Three nano-TiO(2) and one nano-CeO(2) were used. An exposure system was set up using VitroCell® devices to expose pulmonary cells at the air-liquid interface to aerosols. A549 alveolar cells in monocultures or in co-cultures with THP-1 macrophages were exposed to aerosols in inserts or to suspensions in inserts and in plates. Submerged exposures in inserts were performed, using similar culture conditions and exposure kinetics to the air-liquid interface, to provide accurate comparisons between the methods. Exposure in plates using classical culture and exposure conditions was performed to provide comparable results with classical submerged exposure studies. The biological activity of the cells (inflammation, cell viability, oxidative stress) was assessed at 24 h and comparisons of the nanomaterial toxicities between exposure methods were performed. RESULTS: Deposited doses of nanomaterials achieved using our aerosol exposure system were sufficient to observe adverse effects. Co-cultures were more sensitive than monocultures and biological responses were usually observed at lower doses at the air-liquid interface than in submerged conditions. Nevertheless, the general ranking of the nanomaterials according to their toxicity was similar across the different exposure methods used. CONCLUSIONS: We showed that exposure of cells at the air-liquid interface represents a valid and sensitive method to assess the toxicity of several poorly soluble nanomaterials. We underlined the importance of the cellular model used and offer the possibility to deal with low deposition doses by using more sensitive and physiologic cellular models. This brings perspectives towards the use of relevant in vitro methods of exposure to assess nanomaterial toxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0171-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-51372112016-12-15 Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions Loret, Thomas Peyret, Emmanuel Dubreuil, Marielle Aguerre-Chariol, Olivier Bressot, Christophe le Bihan, Olivier Amodeo, Tanguy Trouiller, Bénédicte Braun, Anne Egles, Christophe Lacroix, Ghislaine Part Fibre Toxicol Research BACKGROUND: Recently, much progress has been made to develop more physiologic in vitro models of the respiratory system and improve in vitro simulation of particle exposure through inhalation. Nevertheless, the field of nanotoxicology still suffers from a lack of relevant in vitro models and exposure methods to predict accurately the effects observed in vivo, especially after respiratory exposure. In this context, the aim of our study was to evaluate if exposing pulmonary cells at the air-liquid interface to aerosols of inhalable and poorly soluble nanomaterials generates different toxicity patterns and/or biological activation levels compared to classic submerged exposures to suspensions. Three nano-TiO(2) and one nano-CeO(2) were used. An exposure system was set up using VitroCell® devices to expose pulmonary cells at the air-liquid interface to aerosols. A549 alveolar cells in monocultures or in co-cultures with THP-1 macrophages were exposed to aerosols in inserts or to suspensions in inserts and in plates. Submerged exposures in inserts were performed, using similar culture conditions and exposure kinetics to the air-liquid interface, to provide accurate comparisons between the methods. Exposure in plates using classical culture and exposure conditions was performed to provide comparable results with classical submerged exposure studies. The biological activity of the cells (inflammation, cell viability, oxidative stress) was assessed at 24 h and comparisons of the nanomaterial toxicities between exposure methods were performed. RESULTS: Deposited doses of nanomaterials achieved using our aerosol exposure system were sufficient to observe adverse effects. Co-cultures were more sensitive than monocultures and biological responses were usually observed at lower doses at the air-liquid interface than in submerged conditions. Nevertheless, the general ranking of the nanomaterials according to their toxicity was similar across the different exposure methods used. CONCLUSIONS: We showed that exposure of cells at the air-liquid interface represents a valid and sensitive method to assess the toxicity of several poorly soluble nanomaterials. We underlined the importance of the cellular model used and offer the possibility to deal with low deposition doses by using more sensitive and physiologic cellular models. This brings perspectives towards the use of relevant in vitro methods of exposure to assess nanomaterial toxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0171-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-03 /pmc/articles/PMC5137211/ /pubmed/27919268 http://dx.doi.org/10.1186/s12989-016-0171-3 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Loret, Thomas
Peyret, Emmanuel
Dubreuil, Marielle
Aguerre-Chariol, Olivier
Bressot, Christophe
le Bihan, Olivier
Amodeo, Tanguy
Trouiller, Bénédicte
Braun, Anne
Egles, Christophe
Lacroix, Ghislaine
Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title_full Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title_fullStr Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title_full_unstemmed Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title_short Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
title_sort air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137211/
https://www.ncbi.nlm.nih.gov/pubmed/27919268
http://dx.doi.org/10.1186/s12989-016-0171-3
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