The neuroprotective effect of lamotrigine against glutamate excitotoxicity in SH-SY5Y human neuroblastoma cells

Year 2020, Volume: 33 Issue: 3, 146 - 152, 23.10.2020

Berna Terzıoglu Bebıtoglu Elif Oguz Nazife Gokce Acet Ajla Hodzıc Fatime Temel Saniye Ada Andac Kılıckap

https://doi.org/10.5472/marumj.816319

Cited By: 2

Abstract

Objective: Glutamate-induced excitotoxicity has a role in the pathophysiology of neurodegenerative disorders. Lamotrigine, an
antiepileptic drug, also used to treat bipolar disorders, may be protective against excitotoxic insult. The aim of the study was to
investigate the neuroprotective effect of lamotrigine against the glutamate excitotoxicity in SH-SY5Y cell line.
Materials and Methods: SH-SY5Y human neuroblastoma cells were pre-treated with lamotrigine (50-100-150 μM) prior to exposure
to 15 mM glutamate. The 3-(4,5-dimethythiazol – 2-yl)-2,5 – diphenyl tetrazolium bromide (MTT) assay was performed to determine
cell viability. The anti-oxidant effect of lamotrigine and the role of inflammatory parameters were determined by measuring superoxide
dismutase (SOD), hydrogen peroxide (H2O2), IL-1β, IL-6 and TNF-α.
Results: Intracellular calcium levels and lactate dehydrogenase (LDH) activity increased in glutamate exposed cells. Pre-treatment of
cells with MK-801 showed no protective features against glutamate excitotoxicity. Treatment with 100 μM lamotrigine was effective
in increasing the viability of glutamate exposed cells and in reducing H2O2 increase in these cells. The SOD activity increased by
lamotrigine treated cells exposed to glutamate. IL-1β, IL-6 and TNF-α levels increased after induction with glutamate and attenuated
by lamotrigine.
Conclusion: Overall, our results confirmed the critical role of inflammation and oxidative stress in glutamate-induced excitotoxicity
and lamotrigine may exert a protective effect.
Keywords: Lamotrigine, Glutamate excitotoxicity,

Keywords

Lamotrigine, Glutamate excitotoxicity, SH-SY5Y, Oxidative stress parameter, Cytokines, MK-801

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