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

• Published in: Brain research 2012-01, Vol.1430 (9), p.101-111
• Main Authors: Dalla Corte, Cristiane L, Bastos, Luíza L, Dobrachinski, Fernando, Rocha, João B.T, Soares, Félix A.A
• Format: Article
• Language: English
• Subjects: Animals; antioxidant activity; antioxidants; Antioxidants - pharmacology; Azoles - pharmacology; Benzene Derivatives - pharmacology; Biological and medical sciences; biphenyl; brain; Brain - drug effects; Brain - physiology; Brain Diseases, Metabolic - drug therapy; Brain Diseases, Metabolic - physiopathology; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination - methods; Excitotoxicity; Glutamate; glutamic acid; Glutamic Acid - metabolism; Glutamic Acid - physiology; Glutamic Acid - toxicity; Guanosine; Guanosine - pharmacology; Male; Medical sciences; Neurology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; Neurotoxins - antagonists & inhibitors; Neurotoxins - toxicity; Organ Culture Techniques; Organoselenium compound; Organoselenium Compounds - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; protective effect; Rats; Rats, Wistar; reactive oxygen species; therapeutics
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.10.049

Abstract 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 [3 H]-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 [3 H]-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.