Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

© 2015 Elsevier Inc. Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they ca...

Descripción completa

Detalles Bibliográficos
Autores: Regueiro, Jorge, Olguín, Nair, Simal-Gándara, Jesús, Suñol, Cristina
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/124769
Acceso en línea:http://hdl.handle.net/10261/124769
Access Level:acceso abierto
Palabra clave:Cortical neurons
Fungicides
Neurotoxicity
Calcium channels
Mitochondrial membrane potential
Strobilurin
fungicides
mitochondrial membrane potential
strobilurin
id ES_89d3494590fdc876de4ee666f04d2658
oai_identifier_str oai:digital.csic.es:10261/124769
network_acronym_str ES
network_name_str España
repository_id_str
spelling Toxicity evaluation of new agricultural fungicides in primary cultured cortical neuronsRegueiro, JorgeOlguín, NairSimal-Gándara, JesúsSuñol, CristinaCortical neuronsFungicidesNeurotoxicityCalcium channelsMitochondrial membrane potentialStrobilurinCortical neuronsfungicidesNeurotoxicityCalcium channelsmitochondrial membrane potentialstrobilurin© 2015 Elsevier Inc. Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce.In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100μM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca2+]i and strong depolarization of mitochondrial membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo.This research was supported by the projects PI10/00453 and PI13/01252 from the Instituto de Salud Carlos III cofinanced with European Social Funds “A Way to build Europe” and AGL2011-30378-C03-01 of the Spanish Ministries of Health, and Science and Innovation, respectively. J. R. would like to acknowledge the Ministry of Science and Innovation of Spain for his Juan de la Cierva contract. N.O. is recipient of a CSIC JAE-Doc contract from the “Junta para la Ampliación de Estudios” Program cofinanced with European Social FundsPeer ReviewedAcademic PressInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)Ministerio de Sanidad, Servicios Sociales e Igualdad (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520152015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/124769reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.envres.2015.03.013Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1247692026-05-22T06:33:51Z
dc.title.none.fl_str_mv Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
title Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
spellingShingle Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
Regueiro, Jorge
Cortical neurons
Fungicides
Neurotoxicity
Calcium channels
Mitochondrial membrane potential
Strobilurin
Cortical neurons
fungicides
Neurotoxicity
Calcium channels
mitochondrial membrane potential
strobilurin
title_short Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
title_full Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
title_fullStr Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
title_full_unstemmed Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
title_sort Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons
dc.creator.none.fl_str_mv Regueiro, Jorge
Olguín, Nair
Simal-Gándara, Jesús
Suñol, Cristina
author Regueiro, Jorge
author_facet Regueiro, Jorge
Olguín, Nair
Simal-Gándara, Jesús
Suñol, Cristina
author_role author
author2 Olguín, Nair
Simal-Gándara, Jesús
Suñol, Cristina
author2_role author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cortical neurons
Fungicides
Neurotoxicity
Calcium channels
Mitochondrial membrane potential
Strobilurin
Cortical neurons
fungicides
Neurotoxicity
Calcium channels
mitochondrial membrane potential
strobilurin
topic Cortical neurons
Fungicides
Neurotoxicity
Calcium channels
Mitochondrial membrane potential
Strobilurin
Cortical neurons
fungicides
Neurotoxicity
Calcium channels
mitochondrial membrane potential
strobilurin
description © 2015 Elsevier Inc. Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce.In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100μM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca2+]i and strong depolarization of mitochondrial membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/124769
url http://hdl.handle.net/10261/124769
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.envres.2015.03.013
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
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_ 1869412655877324800
score 15,198674

Similares en LA Referencia