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Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

2013-12Journal article Open access
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dc.contributor.authorMorte, Maria I.
dc.contributor.authorCarreira, Bruno P.
dc.contributor.authorFalcao, Maria J.
dc.contributor.authorAmbrosio, Antonio F.
dc.contributor.authorSoares-da-Silva, Patricio
dc.contributor.authorAraújo, Inês
dc.contributor.authorCarvalho, Caetana M.
dc.date.accessioned2018-12-07T14:52:49Z
dc.date.available2018-12-07T14:52:49Z
dc.date.issued2013-12
dc.description.abstractIn this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3 mM, for 24 h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK. These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent. (C) 2013 Elsevier Ltd. All rights reserved.
dc.description.sponsorshipFoundation for Science and Technology, Portugal [SFRH/BD/38127/2007, SFRH/BD/17196/2004]; BIAL-Portela & Ca, S.A., S. Mamede do Coronado, Portugal
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.tiv.2013.09.008
dc.identifier.issn0887-2333
dc.identifier.urihttp://hdl.handle.net/10400.1/11222
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPergamon-Elsevier Science Ltd
dc.relationEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectEslicarbazepine-Acetate Bia-2-093
dc.subjectApoptosis-inducing factor
dc.subjectSignal-regulated kinase
dc.subjectGated sodium-channels
dc.subjectMethyl-D-Aspartate
dc.subjectMood stabilizers
dc.subjectDeveloping brain
dc.subjectProtein-Kinase
dc.subjectCell-death
dc.subjectHealthy-volunteers
dc.titleEvaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F38127%2F2007/PT
oaire.citation.endPage2202
oaire.citation.issue8
oaire.citation.startPage2193
oaire.citation.titleToxicology in Vitro
oaire.citation.volume27
person.familyNamePombinho de Araújo
person.givenNameInês Maria
person.identifierF-4703-2012
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id56271084100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication.latestForDiscovery1d0c21f4-0f4b-4589-8412-fe1079419774
relation.isProjectOfPublication5401f4f8-66b5-4015-a546-c6ec80c50666
relation.isProjectOfPublication.latestForDiscovery5401f4f8-66b5-4015-a546-c6ec80c50666

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