Please use this identifier to cite or link to this item: 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

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

SCOPUSTM   
Citations

12
checked on Nov 4, 2024

WEB OF SCIENCETM
Citations

9
checked on Nov 2, 2024

Page view(s)

326
checked on Nov 5, 2024

Download(s)

316
checked on Nov 5, 2024

Google ScholarTM

Check

Altmetric

Altmetric


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