Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants

Organophosphate flame retardants (OPFRs) are widely used as additives in plastics, electronics, and construction materials due to their flame-retardant properties. However, previous evidence suggests that OPFRs may pose potential respiratory health risks, including airway hyperresponsiveness, impair...

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Autores: Pyambri, Maryam, Pavlidou, Athina, Lacorte Bruguera, Silvia, Jaumot, Joaquim, Bedia, Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/391935
Acceso en línea:http://hdl.handle.net/10261/391935
https://api.elsevier.com/content/abstract/scopus_id/105006997061
Access Level:acceso abierto
Palabra clave:Phenotype
Cell cultures
Lipidomics
Lung health
Organophosphate flame retardants (OPFRs)
http://metadata.un.org/sdg/11
http://metadata.un.org/sdg/9
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation
Make cities and human settlements inclusive, safe, resilient and sustainable
Ensure sustainable consumption and production patterns
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spelling Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardantsPyambri, MaryamPavlidou, AthinaLacorte Bruguera, SilviaJaumot, JoaquimBedia, CarmenPhenotypeCell culturesLipidomicsLung healthOrganophosphate flame retardants (OPFRs)http://metadata.un.org/sdg/11http://metadata.un.org/sdg/9http://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesBuild resilient infrastructure, promote inclusive and sustainable industrialization and foster innovationMake cities and human settlements inclusive, safe, resilient and sustainableEnsure sustainable consumption and production patternsOrganophosphate flame retardants (OPFRs) are widely used as additives in plastics, electronics, and construction materials due to their flame-retardant properties. However, previous evidence suggests that OPFRs may pose potential respiratory health risks, including airway hyperresponsiveness, impaired lung function, and potential carcinogenic effects. This study evaluated the effects of seven OPFRs-TBOEP, TPhP, EHDPhP, TDCPP, TEHP, TCP, and TCEP-on the phenotype and lipidomic profile of A549 lung cancer cells, using both 2D and 3D culture models. TDCPP and TPhP significantly reduced cell viability, while TBOEP caused the highest increase in reactive oxygen species (ROS), followed by TPhP, TDCPP, and TCP. Moreover, TPhP, TDCPP, EHDPhP, and TBOEP also elevated the levels of pro-inflammatory cytokine interleukin-8 (IL-8). The lipidomic analysis of 3D cell spheroids exposed to OPFRs for 72 h revealed distinct lipid profiles for each compound at low (25 μM) and high (100 μM) doses. Common features were observed, particularly at high doses, including significant increases in triacylglycerol, diacylglycerol, ceramide, ether-linked phosphatidylethanolamine, and phosphatidylinositol species. These effects were generally more pronounced for TPhP, TDCPP, EHDPhP, TCP, and TBOEP. The accumulation of triglycerides, indicative of augmented energy storage, was confirmed by the visualization of lipid droplets formation. Results suggest disruptions in key toxicological pathways, including oxidative stress, inflammatory signaling (IL-8 upregulation), and apoptosis (ceramide accumulation), all implicated in lung diseases, such as COPD and fibrosis. These results provide a basis for assessing the health risks associated with OPFRs, highlighting the need for further research on chronic low-dose exposure levels.This research was funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033, Grants CEX2018-000794-S, and PID2022-137766NB-I00.Peer reviewedElsevierMinisterio de Ciencia e Innovación (España)0000-0002-5836-66170000-0003-4584-5843Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/391935https://api.elsevier.com/content/abstract/scopus_id/105006997061reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MCIN/AEI/10.13039Chemistry and physics of lipidshttps://doi.org/10.1016/j.chemphyslip.2025.105508Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3919352026-05-22T06:33:51Z
dc.title.none.fl_str_mv Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
title Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
spellingShingle Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
Pyambri, Maryam
Phenotype
Cell cultures
Lipidomics
Lung health
Organophosphate flame retardants (OPFRs)
http://metadata.un.org/sdg/11
http://metadata.un.org/sdg/9
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation
Make cities and human settlements inclusive, safe, resilient and sustainable
Ensure sustainable consumption and production patterns
title_short Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
title_full Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
title_fullStr Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
title_full_unstemmed Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
title_sort Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants
dc.creator.none.fl_str_mv Pyambri, Maryam
Pavlidou, Athina
Lacorte Bruguera, Silvia
Jaumot, Joaquim
Bedia, Carmen
author Pyambri, Maryam
author_facet Pyambri, Maryam
Pavlidou, Athina
Lacorte Bruguera, Silvia
Jaumot, Joaquim
Bedia, Carmen
author_role author
author2 Pavlidou, Athina
Lacorte Bruguera, Silvia
Jaumot, Joaquim
Bedia, Carmen
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
0000-0002-5836-6617
0000-0003-4584-5843
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Phenotype
Cell cultures
Lipidomics
Lung health
Organophosphate flame retardants (OPFRs)
http://metadata.un.org/sdg/11
http://metadata.un.org/sdg/9
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation
Make cities and human settlements inclusive, safe, resilient and sustainable
Ensure sustainable consumption and production patterns
topic Phenotype
Cell cultures
Lipidomics
Lung health
Organophosphate flame retardants (OPFRs)
http://metadata.un.org/sdg/11
http://metadata.un.org/sdg/9
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation
Make cities and human settlements inclusive, safe, resilient and sustainable
Ensure sustainable consumption and production patterns
description Organophosphate flame retardants (OPFRs) are widely used as additives in plastics, electronics, and construction materials due to their flame-retardant properties. However, previous evidence suggests that OPFRs may pose potential respiratory health risks, including airway hyperresponsiveness, impaired lung function, and potential carcinogenic effects. This study evaluated the effects of seven OPFRs-TBOEP, TPhP, EHDPhP, TDCPP, TEHP, TCP, and TCEP-on the phenotype and lipidomic profile of A549 lung cancer cells, using both 2D and 3D culture models. TDCPP and TPhP significantly reduced cell viability, while TBOEP caused the highest increase in reactive oxygen species (ROS), followed by TPhP, TDCPP, and TCP. Moreover, TPhP, TDCPP, EHDPhP, and TBOEP also elevated the levels of pro-inflammatory cytokine interleukin-8 (IL-8). The lipidomic analysis of 3D cell spheroids exposed to OPFRs for 72 h revealed distinct lipid profiles for each compound at low (25 μM) and high (100 μM) doses. Common features were observed, particularly at high doses, including significant increases in triacylglycerol, diacylglycerol, ceramide, ether-linked phosphatidylethanolamine, and phosphatidylinositol species. These effects were generally more pronounced for TPhP, TDCPP, EHDPhP, TCP, and TBOEP. The accumulation of triglycerides, indicative of augmented energy storage, was confirmed by the visualization of lipid droplets formation. Results suggest disruptions in key toxicological pathways, including oxidative stress, inflammatory signaling (IL-8 upregulation), and apoptosis (ceramide accumulation), all implicated in lung diseases, such as COPD and fibrosis. These results provide a basis for assessing the health risks associated with OPFRs, highlighting the need for further research on chronic low-dose exposure levels.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/391935
https://api.elsevier.com/content/abstract/scopus_id/105006997061
url http://hdl.handle.net/10261/391935
https://api.elsevier.com/content/abstract/scopus_id/105006997061
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MCIN/AEI/10.13039
Chemistry and physics of lipids
https://doi.org/10.1016/j.chemphyslip.2025.105508
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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