GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity

Autores
Galofré, Mireia; Babot, Zoila; Garcia, Daniel Asmed; Iraola, Susana; Rodriguez Farré, Eduard; Forsby, Anna; Suñol, Cristina
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of rodent and human toxicity. The nervous system is particularly vulnerable to chemical exposure which may result in different toxicity features. Acute human toxicity related to adverse neuronal function is usually a result of over-excitation or depression of the nervous system. The major molecular and cellular mechanisms involved in such reactions include GABAergic, glutamatergic and cholinergic neurotransmission, regulation of cell and mitochondrial membrane potential, and those critical for maintaining central nervous system functionality, such as controlling cell energy. In this work, a set of chemicals that are used in pharmacy, industry, biocide treatments or are often abused by drug users are tested for their effects on GABAA receptor activity, GABA and glutamate transport, cell membrane potential and cell viability in primary neuronal cultures. GABAA receptor function was inhibited by compounds for which seizures have been observed after severe human poisoning. Commonly abused drugs inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane potential. The GABAA receptor, GABA uptake and cell membrane potential assays were those that identified the highest number of chemicals as toxic at low concentrations. These results show that in vitro cell assays may identify compounds that produce acute neurotoxicity in humans, provided that in vitro models expressing neuronal targets relevant for acute neural dysfunctions are used.
Fil: Galofré, Mireia. Consejo Superior de Investigaciones Científicas; España
Fil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; España
Fil: Iraola, Susana. Consejo Superior de Investigaciones Científicas; España
Fil: Rodriguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; España
Fil: Forsby, Anna. Stockholms Universitet; Suecia
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
Materia
Cell Membrane Potential
Gaba
Gabaa Receptor
In Vitro
Neurotoxicity
Primary Neuronal Cultures
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/64566
Acceder
id CONICETDig_d0acc3105db57ba157495145e08515a2
oai_identifier_str oai:ri.conicet.gov.ar:11336/64566
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicityGalofré, MireiaBabot, ZoilaGarcia, Daniel AsmedIraola, SusanaRodriguez Farré, EduardForsby, AnnaSuñol, CristinaCell Membrane PotentialGabaGabaa ReceptorIn VitroNeurotoxicityPrimary Neuronal Cultureshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of rodent and human toxicity. The nervous system is particularly vulnerable to chemical exposure which may result in different toxicity features. Acute human toxicity related to adverse neuronal function is usually a result of over-excitation or depression of the nervous system. The major molecular and cellular mechanisms involved in such reactions include GABAergic, glutamatergic and cholinergic neurotransmission, regulation of cell and mitochondrial membrane potential, and those critical for maintaining central nervous system functionality, such as controlling cell energy. In this work, a set of chemicals that are used in pharmacy, industry, biocide treatments or are often abused by drug users are tested for their effects on GABAA receptor activity, GABA and glutamate transport, cell membrane potential and cell viability in primary neuronal cultures. GABAA receptor function was inhibited by compounds for which seizures have been observed after severe human poisoning. Commonly abused drugs inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane potential. The GABAA receptor, GABA uptake and cell membrane potential assays were those that identified the highest number of chemicals as toxic at low concentrations. These results show that in vitro cell assays may identify compounds that produce acute neurotoxicity in humans, provided that in vitro models expressing neuronal targets relevant for acute neural dysfunctions are used.Fil: Galofré, Mireia. Consejo Superior de Investigaciones Científicas; EspañaFil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; EspañaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; EspañaFil: Iraola, Susana. Consejo Superior de Investigaciones Científicas; EspañaFil: Rodriguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; EspañaFil: Forsby, Anna. Stockholms Universitet; SueciaFil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; EspañaPergamon-Elsevier Science Ltd2010-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/64566Galofré, Mireia; Babot, Zoila; Garcia, Daniel Asmed; Iraola, Susana; Rodriguez Farré, Eduard; et al.; GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity; Pergamon-Elsevier Science Ltd; Neurotoxicology and Teratology; 32; 1; 2-2010; 52-610892-0362CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0892036209000142info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ntt.2009.01.010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:37:12Zoai:ri.conicet.gov.ar:11336/64566instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:37:12.818CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
title GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
spellingShingle GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
Galofré, Mireia
Cell Membrane Potential
Gaba
Gabaa Receptor
In Vitro
Neurotoxicity
Primary Neuronal Cultures
title_short GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
title_full GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
title_fullStr GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
title_full_unstemmed GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
title_sort GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
dc.creator.none.fl_str_mv Galofré, Mireia
Babot, Zoila
Garcia, Daniel Asmed
Iraola, Susana
Rodriguez Farré, Eduard
Forsby, Anna
Suñol, Cristina
author Galofré, Mireia
author_facet Galofré, Mireia
Babot, Zoila
Garcia, Daniel Asmed
Iraola, Susana
Rodriguez Farré, Eduard
Forsby, Anna
Suñol, Cristina
author_role author
author2 Babot, Zoila
Garcia, Daniel Asmed
Iraola, Susana
Rodriguez Farré, Eduard
Forsby, Anna
Suñol, Cristina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cell Membrane Potential
Gaba
Gabaa Receptor
In Vitro
Neurotoxicity
Primary Neuronal Cultures
topic Cell Membrane Potential
Gaba
Gabaa Receptor
In Vitro
Neurotoxicity
Primary Neuronal Cultures
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of rodent and human toxicity. The nervous system is particularly vulnerable to chemical exposure which may result in different toxicity features. Acute human toxicity related to adverse neuronal function is usually a result of over-excitation or depression of the nervous system. The major molecular and cellular mechanisms involved in such reactions include GABAergic, glutamatergic and cholinergic neurotransmission, regulation of cell and mitochondrial membrane potential, and those critical for maintaining central nervous system functionality, such as controlling cell energy. In this work, a set of chemicals that are used in pharmacy, industry, biocide treatments or are often abused by drug users are tested for their effects on GABAA receptor activity, GABA and glutamate transport, cell membrane potential and cell viability in primary neuronal cultures. GABAA receptor function was inhibited by compounds for which seizures have been observed after severe human poisoning. Commonly abused drugs inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane potential. The GABAA receptor, GABA uptake and cell membrane potential assays were those that identified the highest number of chemicals as toxic at low concentrations. These results show that in vitro cell assays may identify compounds that produce acute neurotoxicity in humans, provided that in vitro models expressing neuronal targets relevant for acute neural dysfunctions are used.
Fil: Galofré, Mireia. Consejo Superior de Investigaciones Científicas; España
Fil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Consejo Superior de Investigaciones Científicas; España
Fil: Iraola, Susana. Consejo Superior de Investigaciones Científicas; España
Fil: Rodriguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; España
Fil: Forsby, Anna. Stockholms Universitet; Suecia
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
description Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of rodent and human toxicity. The nervous system is particularly vulnerable to chemical exposure which may result in different toxicity features. Acute human toxicity related to adverse neuronal function is usually a result of over-excitation or depression of the nervous system. The major molecular and cellular mechanisms involved in such reactions include GABAergic, glutamatergic and cholinergic neurotransmission, regulation of cell and mitochondrial membrane potential, and those critical for maintaining central nervous system functionality, such as controlling cell energy. In this work, a set of chemicals that are used in pharmacy, industry, biocide treatments or are often abused by drug users are tested for their effects on GABAA receptor activity, GABA and glutamate transport, cell membrane potential and cell viability in primary neuronal cultures. GABAA receptor function was inhibited by compounds for which seizures have been observed after severe human poisoning. Commonly abused drugs inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane potential. The GABAA receptor, GABA uptake and cell membrane potential assays were those that identified the highest number of chemicals as toxic at low concentrations. These results show that in vitro cell assays may identify compounds that produce acute neurotoxicity in humans, provided that in vitro models expressing neuronal targets relevant for acute neural dysfunctions are used.
publishDate 2010
dc.date.none.fl_str_mv 2010-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/64566
Galofré, Mireia; Babot, Zoila; Garcia, Daniel Asmed; Iraola, Susana; Rodriguez Farré, Eduard; et al.; GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity; Pergamon-Elsevier Science Ltd; Neurotoxicology and Teratology; 32; 1; 2-2010; 52-61
0892-0362
CONICET Digital
CONICET
url http://hdl.handle.net/11336/64566
identifier_str_mv Galofré, Mireia; Babot, Zoila; Garcia, Daniel Asmed; Iraola, Susana; Rodriguez Farré, Eduard; et al.; GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity; Pergamon-Elsevier Science Ltd; Neurotoxicology and Teratology; 32; 1; 2-2010; 52-61
0892-0362
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0892036209000142
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ntt.2009.01.010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082842998603776
score 13.22299

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