Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots
With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of N...
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MDPI AG
2021-01-01
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Series: | Nanomaterials |
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Online Access: | https://www.mdpi.com/2079-4991/11/1/180 |
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author | Maud Weiss Jiahui Fan Mickaël Claudel Luc Lebeau Françoise Pons Carole Ronzani |
author_facet | Maud Weiss Jiahui Fan Mickaël Claudel Luc Lebeau Françoise Pons Carole Ronzani |
author_sort | Maud Weiss |
collection | DOAJ |
description | With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury. |
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issn | 2079-4991 |
language | English |
last_indexed | 2024-03-09T04:58:49Z |
publishDate | 2021-01-01 |
publisher | MDPI AG |
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series | Nanomaterials |
spelling | doaj.art-270e9f32ba264caabd534c75ffa1447c2023-12-03T13:01:59ZengMDPI AGNanomaterials2079-49912021-01-0111118010.3390/nano11010180Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon DotsMaud Weiss0Jiahui Fan1Mickaël Claudel2Luc Lebeau3Françoise Pons4Carole Ronzani5Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceLaboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceLaboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceLaboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceLaboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceLaboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, FranceWith the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.https://www.mdpi.com/2079-4991/11/1/180adverse outcome pathwaynanoparticlescarbon dotsnanotoxicologylung toxicitylysosome |
spellingShingle | Maud Weiss Jiahui Fan Mickaël Claudel Luc Lebeau Françoise Pons Carole Ronzani Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots Nanomaterials adverse outcome pathway nanoparticles carbon dots nanotoxicology lung toxicity lysosome |
title | Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots |
title_full | Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots |
title_fullStr | Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots |
title_full_unstemmed | Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots |
title_short | Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots |
title_sort | combined in vitro and in vivo approaches to propose a putative adverse outcome pathway for acute lung inflammation induced by nanoparticles a study on carbon dots |
topic | adverse outcome pathway nanoparticles carbon dots nanotoxicology lung toxicity lysosome |
url | https://www.mdpi.com/2079-4991/11/1/180 |
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