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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
dc.conicet.fuente individual


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)