Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/24969
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dc.contributor.authorMorte, Maria I.-
dc.contributor.authorCarreira, Bruno P.-
dc.contributor.authorFalcão, Maria J.-
dc.contributor.authorAmbrosio, António M.-
dc.contributor.authorSoares-da-Silva, Patrício-
dc.contributor.authorAraújo, Inês M.-
dc.contributor.authorCarvalho, Caetana M.-
dc.date.accessioned2014-01-29T15:53:33Z-
dc.date.available2014-01-29T15:53:33Z-
dc.date.issued2013-
dc.identifier.issn0887-2333-
dc.identifier.urihttp://hdl.handle.net/10316/24969-
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 extracellularregulated 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.por
dc.description.sponsorshipThis work was funded by BIAL-Portela & Cª, S.A., S. Mamede do Coronado, Portugal. MIM and BPC were supported by Foundation for Science and Technology, Portugal (SFRH/BD/38127/2007 and SFRH/BD/17196/2004).por
dc.language.isoengpor
dc.publisherElsevier Ltd.por
dc.rightsopenAccesspor
dc.subjectEslicarbazepinepor
dc.subjectCarbamazepinepor
dc.subjectOxcarbazepinepor
dc.subjectLamotriginepor
dc.subjectValproatepor
dc.subjectNeurotoxicitypor
dc.titleEvaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neuronspor
dc.typearticlepor
degois.publication.firstPage2193por
degois.publication.lastPage2202por
degois.publication.issue8por
degois.publication.titleToxicology in Vitropor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0887233313002178#por
dc.peerreviewedYespor
degois.publication.volume27por
item.grantfulltextopen-
item.languageiso639-1en-
item.fulltextCom Texto completo-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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