Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/24969
DC Field | Value | Language |
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dc.contributor.author | Morte, Maria I. | - |
dc.contributor.author | Carreira, Bruno P. | - |
dc.contributor.author | Falcão, Maria J. | - |
dc.contributor.author | Ambrosio, António M. | - |
dc.contributor.author | Soares-da-Silva, Patrício | - |
dc.contributor.author | Araújo, Inês M. | - |
dc.contributor.author | Carvalho, Caetana M. | - |
dc.date.accessioned | 2014-01-29T15:53:33Z | - |
dc.date.available | 2014-01-29T15:53:33Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0887-2333 | - |
dc.identifier.uri | https://hdl.handle.net/10316/24969 | - |
dc.description.abstract | In 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.sponsorship | This 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.iso | eng | por |
dc.publisher | Elsevier Ltd. | por |
dc.rights | openAccess | por |
dc.subject | Eslicarbazepine | por |
dc.subject | Carbamazepine | por |
dc.subject | Oxcarbazepine | por |
dc.subject | Lamotrigine | por |
dc.subject | Valproate | por |
dc.subject | Neurotoxicity | por |
dc.title | Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons | por |
dc.type | article | por |
degois.publication.firstPage | 2193 | por |
degois.publication.lastPage | 2202 | por |
degois.publication.issue | 8 | por |
degois.publication.title | Toxicology in Vitro | por |
dc.relation.publisherversion | http://www.sciencedirect.com/science/article/pii/S0887233313002178# | por |
dc.peerreviewed | Yes | por |
dc.identifier.doi | 10.1016/j.tiv.2013.09.008 | - |
degois.publication.volume | 27 | por |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-7874-6545 | - |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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1-s2.0-S0887233313002178-main.pdf | 1.54 MB | Adobe PDF | View/Open |
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