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

Abstract

Objective: Glutamate-induced excitotoxicity has a role in the pathophysiology of neurodegenerative disorders. Lamotrigine, anantiepileptic drug, also used to treat bipolar disorders, may be protective against excitotoxic insult. The aim of the study was toinvestigate 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 exposureto 15 mM glutamate. The 3-(4,5-dimethythiazol – 2-yl)-2,5 – diphenyl tetrazolium bromide (MTT) assay was performed to determinecell viability. The anti-oxidant effect of lamotrigine and the role of inflammatory parameters were determined by measuring superoxidedismutase (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 ofcells with MK-801 showed no protective features against glutamate excitotoxicity. Treatment with 100 µM lamotrigine was effectivein increasing the viability of glutamate exposed cells and in reducing H2O2 increase in these cells. The SOD activity increased bylamotrigine treated cells exposed to glutamate. IL-1β, IL-6 and TNF-α levels increased after induction with glutamate and attenuatedby lamotrigine.Conclusion: Overall, our results confirmed the critical role of inflammation and oxidative stress in glutamate-induced excitotoxicityand lamotrigine may exert a protective effect.