Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB)
The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. T...
| Autores: | , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/281516 |
| Acesso em linha: | http://hdl.handle.net/10261/281516 https://api.elsevier.com/content/abstract/scopus_id/85139013222 |
| Access Level: | acceso abierto |
| Palavra-chave: | Pyrethroids Blood-brain-barrier Chlorpyrifos Cyfluthrin Efflux ratio HCMEC/D3 Insecticides Permeability Permethrin |
| id |
ES_5ecd8a2fef070eb5a878e70cef2134ed |
|---|---|
| oai_identifier_str |
oai:digital.csic.es:10261/281516 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB)Deepika, DeepikaKumar, SauravBravo, NataliaEsplugas, RoserCapodiferro, MarcoSharma, Raju PrasadSchuhmacher, MartaGrimalt, Joan O.Blanco, JordiKumar, VikasPyrethroidsBlood-brain-barrierChlorpyrifosCyfluthrinEfflux ratioHCMEC/D3InsecticidesPermeabilityPermethrinThe blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and capability to induce BBB dysfunction than among the above-mentioned chemicals. Additionally, the results of the permeation study could be useful to build a human PBPK model using in vitro-to-in vivo extrapolation approach.This study was financially supported by Marie Skłodowska-Curie “Neurosome Project” under the grant agreement No. 766251. This publication reflects only the authors' views. The Community and other funding organizations are not liable for any use made of the information contained therein.Peer reviewedElsevierEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/281516https://api.elsevier.com/content/abstract/scopus_id/85139013222reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/766251Neurotoxicologyhttps://doi.org/10.1016/j.neuro.2022.09.010Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2815162026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| title |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| spellingShingle |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) Deepika, Deepika Pyrethroids Blood-brain-barrier Chlorpyrifos Cyfluthrin Efflux ratio HCMEC/D3 Insecticides Permeability Permethrin |
| title_short |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| title_full |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| title_fullStr |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| title_full_unstemmed |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| title_sort |
Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB) |
| dc.creator.none.fl_str_mv |
Deepika, Deepika Kumar, Saurav Bravo, Natalia Esplugas, Roser Capodiferro, Marco Sharma, Raju Prasad Schuhmacher, Marta Grimalt, Joan O. Blanco, Jordi Kumar, Vikas |
| author |
Deepika, Deepika |
| author_facet |
Deepika, Deepika Kumar, Saurav Bravo, Natalia Esplugas, Roser Capodiferro, Marco Sharma, Raju Prasad Schuhmacher, Marta Grimalt, Joan O. Blanco, Jordi Kumar, Vikas |
| author_role |
author |
| author2 |
Kumar, Saurav Bravo, Natalia Esplugas, Roser Capodiferro, Marco Sharma, Raju Prasad Schuhmacher, Marta Grimalt, Joan O. Blanco, Jordi Kumar, Vikas |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
European Commission Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Pyrethroids Blood-brain-barrier Chlorpyrifos Cyfluthrin Efflux ratio HCMEC/D3 Insecticides Permeability Permethrin |
| topic |
Pyrethroids Blood-brain-barrier Chlorpyrifos Cyfluthrin Efflux ratio HCMEC/D3 Insecticides Permeability Permethrin |
| description |
The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and capability to induce BBB dysfunction than among the above-mentioned chemicals. Additionally, the results of the permeation study could be useful to build a human PBPK model using in vitro-to-in vivo extrapolation approach. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 |
| 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/10261/281516 https://api.elsevier.com/content/abstract/scopus_id/85139013222 |
| url |
http://hdl.handle.net/10261/281516 https://api.elsevier.com/content/abstract/scopus_id/85139013222 |
| 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/EC/H2020/766251 Neurotoxicology https://doi.org/10.1016/j.neuro.2022.09.010 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 |
|
| _version_ |
1869409156452057088 |
| score |
15,81155 |