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|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.
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.||URI:||http://hdl.handle.net/10316/24969||ISSN:||0887-2333||Rights:||openAccess|
|Appears in Collections:||FCTUC Ciências da Vida - Artigos em Revistas Internacionais|
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