Oligoprotective Activity of Levetiracetam against Glutamate Toxicity: An In vitro Study

Abstract

Introduction: The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes. Methods: At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting. Results: LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced reactive oxygen species (ROS) accumulation and malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure. Conclusion: Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.