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https://hdl.handle.net/10316/24969
Title: | Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons | Authors: | Morte, Maria I. Carreira, Bruno P. Falcão, Maria J. Ambrosio, António M. Soares-da-Silva, Patrício Araújo, Inês M. Carvalho, Caetana M. |
Keywords: | Eslicarbazepine; Carbamazepine; Oxcarbazepine; Lamotrigine; Valproate; Neurotoxicity | Issue Date: | 2013 | Publisher: | Elsevier Ltd. | metadata.degois.publication.title: | Toxicology in Vitro | metadata.degois.publication.volume: | 27 | metadata.degois.publication.issue: | 8 | 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. | URI: | https://hdl.handle.net/10316/24969 | ISSN: | 0887-2333 | DOI: | 10.1016/j.tiv.2013.09.008 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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