Research ReportThe combination of organoselenium compounds and guanosine prevents glutamate-induced oxidative stress in different regions of rat brains

This study was designed to investigate the protective effects of the combination of guanosine and 2 organoselenium compounds (ebselen and diphenyl diselenide) against glutamate-induced oxidative stress in different regions of rat brains. Glutamate caused an increase in reactive oxygen species (ROS) generation and a decrease in [3H]-glutamate uptake in striatal, cortical, and hippocampal slices. Guanosine, ebselen, and diphenyl diselenide prevented glutamate-induced ROS production in striatal, cortical and hippocampal slices. The combination of guanosine with organoselenium compounds was more effective against glutamate-induced ROS production than the individual compounds alone. Guanosine prevented [3H]-glutamate uptake inhibition in striatal, cortical, and hippocampal slices. Thus, protection against the harmful effects of glutamate is possibly due to the combination of the antioxidant properties of organoselenium compounds and the stimulatory effect of guanosine on glutamate uptake. In conclusion, the combination of antioxidants and glutamatergic system modulators could be considered a potential therapy against the prooxidant effects of glutamate.

► We tested the effect of guanosine and seleno-compounds on glutamate excitotoxicity. ► Guanosine and seleno-compounds protected against glutamate excitotoxicity. ► Guanosine prevented glutamate uptake inhibition in different brain regions. ► Combining guanosine and seleno-compounds is more effective than the treatments alone. ► Protection is due to antioxidant properties and modulation of glutamatergic system.