Autor(es):
Morte, Maria I. 
; Carreira, Bruno P. ; Falcão, Maria J. ; Ambrosio, António M. ; Soares-da-Silva, Patrício ; Araújo, Inês M. ; Carvalho, Caetana M.
Data: 2013
Identificador Persistente: http://hdl.handle.net/10316/24969
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): Eslicarbazepine; Carbamazepine; Oxcarbazepine; Lamotrigine; Valproate; Neurotoxicity
Descrição
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. 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).
