Please use this identifier to cite or link to this item:
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.
Serial title, monograph or event: Toxicology in Vitro
Volume: 27
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.
ISSN: 0887-2333
DOI: 10.1016/j.tiv.2013.09.008
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
1-s2.0-S0887233313002178-main.pdf1.54 MBAdobe PDFView/Open
Show full item record


checked on Apr 2, 2022

Page view(s)

checked on Aug 18, 2022


checked on Aug 18, 2022

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.