Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity

The cyanotoxin cylindrospermopsin (CYN) has been postulated to cause neurotoxicity, although the studies in this concern are very few. In addition, some studies in vitro indicate its possible effects on development. Furthermore, pesticides can be present in the same environmental samples as cyanotox...

ver descrição completa

Detalhes bibliográficos
Autores: Hinojosa Hidalgo, María Gracia, Johansson, Y., Jos Gallego, Ángeles Mencía, Cameán Fernández, Ana María, Forsby, Anna
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/159810
Acesso em linha:https://hdl.handle.net/11441/159810
https://doi.org/10.1016/j.ecoenv.2023.115804
Access Level:Acceso aberto
Palavra-chave:Chlorpyrifos
Cylindrospermopsin
Developmental neurotoxicity
NAChRs
Neurite outgrowth
Transcriptomics
id ES_ff0fa79e4defce516d7da4d56b9ac677
oai_identifier_str oai:idus.us.es:11441/159810
network_acronym_str ES
network_name_str España
repository_id_str
spelling Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental NeurotoxicityHinojosa Hidalgo, María GraciaJohansson, Y.Jos Gallego, Ángeles MencíaCameán Fernández, Ana MaríaForsby, AnnaChlorpyrifosCylindrospermopsinDevelopmental neurotoxicityNAChRsNeurite outgrowthTranscriptomicsThe cyanotoxin cylindrospermopsin (CYN) has been postulated to cause neurotoxicity, although the studies in this concern are very few. In addition, some studies in vitro indicate its possible effects on development. Furthermore, pesticides can be present in the same environmental samples as cyanotoxins. Therefore, chlorpyrifos (CPF) has been one of the most common pesticides used worldwide. The aim of this report was to study the effects of CYN, isolated and in combination with CPF, in a developmental neurotoxicity in vitro model. The human neuroblastoma SH-SY5Y cell line was exposed during 6 days of differentiation to both toxics to study their effects on cell viability and neurite outgrowth. To further evaluate effects of both toxicants on cholinergic signaling, their agonistic and antagonistic activities on the α7 homomeric nicotinic acetylcholine receptor (nAChR) were studied upon acute exposure. Moreover, a transcriptomic analysis by qPCR was performed after 6 days of CYN-exposure during differentiation. The results showed a concentration-dependent decrease on both cell viability and neurite outgrowth for both toxics isolated, leading to effective concentration 20 (EC20) values of 0.35 µM and 0.097 µM for CYN on cell viability and neurite outgrowth, respectively, and 100 µM and 58 µM for CPF, while the combination demonstrated no significant variations. In addition, 95 µM and 285 µM CPF demonstrated to act as an antagonist to nicotine on the nAChR, although CYN up to 2.4 µM had no effect on the efficacy of these receptors. Additionally, the EC20 for CYN (0.097 µM) on neurite outgrowth downregulated expression of the 5 genes NTNG2 (netrin G2), KCNJ11 (potassium channel), SLC18A3 (vesicular acetylcholine transporter), APOE (apolipoprotein E), and SEMA6B (semaphorin 6B), that are all important for neuronal development. Thus, this study points out the importance of studying the effects of CYN in terms of neurotoxicity and developmental neurotoxicity.Swedish Fund for Research Without Animal Experiments N2018-0004, F2019-0009, F2020-0006Swedish Research Council 2018-03269Ministerio de Economía y Competitividad AGL2015-64558-RMinisterio de Ciencia e Innovación PID2019-104890RB-I00ElsevierNutrición y Bromatología, Toxicología y Medicina LegalSwedish Fund for Research Without Animal ExperimentsSwedish Research CouncilMinisterio de Economía y Competitividad (MINECO). EspañaMinisterio de Ciencia e Innovación (MICIN). España2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/159810https://doi.org/10.1016/j.ecoenv.2023.115804reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésEcotoxicology and Environmental Safety, 269, 115804.N2018-0004F2019-0009F2020-00062018-03269AGL2015-64558-RPID2019-104890RB-I00https://doi.org/10.1016/j.ecoenv.2023.115804info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1598102026-06-17T12:51:07Z
dc.title.none.fl_str_mv Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
title Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
spellingShingle Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
Hinojosa Hidalgo, María Gracia
Chlorpyrifos
Cylindrospermopsin
Developmental neurotoxicity
NAChRs
Neurite outgrowth
Transcriptomics
title_short Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
title_full Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
title_fullStr Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
title_full_unstemmed Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
title_sort Effects of Cylindrospermopsin, Chlorpyrifos and their Combination in a SH-SY5Y Cell Model Concerning Developmental Neurotoxicity
dc.creator.none.fl_str_mv Hinojosa Hidalgo, María Gracia
Johansson, Y.
Jos Gallego, Ángeles Mencía
Cameán Fernández, Ana María
Forsby, Anna
author Hinojosa Hidalgo, María Gracia
author_facet Hinojosa Hidalgo, María Gracia
Johansson, Y.
Jos Gallego, Ángeles Mencía
Cameán Fernández, Ana María
Forsby, Anna
author_role author
author2 Johansson, Y.
Jos Gallego, Ángeles Mencía
Cameán Fernández, Ana María
Forsby, Anna
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Nutrición y Bromatología, Toxicología y Medicina Legal
Swedish Fund for Research Without Animal Experiments
Swedish Research Council
Ministerio de Economía y Competitividad (MINECO). España
Ministerio de Ciencia e Innovación (MICIN). España
dc.subject.none.fl_str_mv Chlorpyrifos
Cylindrospermopsin
Developmental neurotoxicity
NAChRs
Neurite outgrowth
Transcriptomics
topic Chlorpyrifos
Cylindrospermopsin
Developmental neurotoxicity
NAChRs
Neurite outgrowth
Transcriptomics
description The cyanotoxin cylindrospermopsin (CYN) has been postulated to cause neurotoxicity, although the studies in this concern are very few. In addition, some studies in vitro indicate its possible effects on development. Furthermore, pesticides can be present in the same environmental samples as cyanotoxins. Therefore, chlorpyrifos (CPF) has been one of the most common pesticides used worldwide. The aim of this report was to study the effects of CYN, isolated and in combination with CPF, in a developmental neurotoxicity in vitro model. The human neuroblastoma SH-SY5Y cell line was exposed during 6 days of differentiation to both toxics to study their effects on cell viability and neurite outgrowth. To further evaluate effects of both toxicants on cholinergic signaling, their agonistic and antagonistic activities on the α7 homomeric nicotinic acetylcholine receptor (nAChR) were studied upon acute exposure. Moreover, a transcriptomic analysis by qPCR was performed after 6 days of CYN-exposure during differentiation. The results showed a concentration-dependent decrease on both cell viability and neurite outgrowth for both toxics isolated, leading to effective concentration 20 (EC20) values of 0.35 µM and 0.097 µM for CYN on cell viability and neurite outgrowth, respectively, and 100 µM and 58 µM for CPF, while the combination demonstrated no significant variations. In addition, 95 µM and 285 µM CPF demonstrated to act as an antagonist to nicotine on the nAChR, although CYN up to 2.4 µM had no effect on the efficacy of these receptors. Additionally, the EC20 for CYN (0.097 µM) on neurite outgrowth downregulated expression of the 5 genes NTNG2 (netrin G2), KCNJ11 (potassium channel), SLC18A3 (vesicular acetylcholine transporter), APOE (apolipoprotein E), and SEMA6B (semaphorin 6B), that are all important for neuronal development. Thus, this study points out the importance of studying the effects of CYN in terms of neurotoxicity and developmental neurotoxicity.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/159810
https://doi.org/10.1016/j.ecoenv.2023.115804
url https://hdl.handle.net/11441/159810
https://doi.org/10.1016/j.ecoenv.2023.115804
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Ecotoxicology and Environmental Safety, 269, 115804.
N2018-0004
F2019-0009
F2020-0006
2018-03269
AGL2015-64558-R
PID2019-104890RB-I00
https://doi.org/10.1016/j.ecoenv.2023.115804
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425740883165184
score 15.301603

Registros relacionados