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, 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 mu M) 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-1 beta, IL-6 and TNF-alpha. 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 mu M 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-1 beta, IL-6 and TNF-alpha 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.