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dc.contributor.author
Galofré, Mireia
dc.contributor.author
Babot, Zoila
dc.contributor.author
Garcia, Daniel Asmed
dc.contributor.author
Iraola, Susana
dc.contributor.author
Rodriguez Farré, Eduard
dc.contributor.author
Forsby, Anna
dc.contributor.author
Suñol, Cristina
dc.date.available
2018-11-15T19:03:38Z
dc.date.issued
2010-02
dc.identifier.citation
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
dc.identifier.issn
0892-0362
dc.identifier.uri
http://hdl.handle.net/11336/64566
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Cell Membrane Potential
dc.subject
Gaba
dc.subject
Gabaa Receptor
dc.subject
In Vitro
dc.subject
Neurotoxicity
dc.subject
Primary Neuronal Cultures
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-07-11T17:47:08Z
dc.journal.volume
32
dc.journal.number
1
dc.journal.pagination
52-61
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Galofré, Mireia. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
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
dc.description.fil
Fil: Iraola, Susana. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Rodriguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Forsby, Anna. Stockholms Universitet; Suecia
dc.description.fil
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
dc.journal.title
Neurotoxicology and Teratology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0892036209000142
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ntt.2009.01.010


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