Cooperation of non-effective concentration of glutamatergic system modulators and antioxidant against oxidative stress induced by quinolinic acid.
Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been hypothesized as key mechanisms contributing to quinolinic acid (QA)-induced toxicity. Thus, here we investigate if the use of diphenyl diselenide (PhSe)(2), guanosine (GUO) and MK-801, alone or in combination, could protect rat brain slices from QA-induced toxicity. QA (1 mM) increased ROS formation, thiobarbituric acid reactive substances (TBARS) and decreased cell viability after 2 h of exposure. (PhSe)(2) (1 μM) protected against this ROS formation in the cortex and the striatum and also prevented decreases in cell viability induced by QA. (PhSe)(2) (5 μM) prevented ROS formation in the hippocampus. GUO (10 and 100 μM) blocked the increase in ROS formation caused by QA and MK-801 (20 and 100 μM) abolished the pro-oxidant effect of QA. When the noneffective concentrations were used in combination produced a decrease in ROS formation, mainly (PhSe)(2) + GUO and (PhSe)(2) + GUO + MK-801. These results demonstrate that this combination could be effective to avoid toxic effects caused by high concentrations of QA. Furthermore, the data obtained in the ROS formation and cellular viability assays suggest different pathways in amelioration of QA toxicity present in the neurodegenerative process.
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS CEP 97105-900, Brazil.
Fernando
F
Dobrachinski
Luiza Lena
LL
Bastos
Jessika Cristina
JC
Bridi
Cristiane Lenz Dalla
CL
Corte
Daiana Silva
DS
de Ávila
João Batista Teixeira
JB
da Rocha
Félix Alexandre Antunes
FA
Soares
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D006151:Guanosine / Q000494:pharmacology; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology; D016877:Oxidants; D018384:Oxidative Stress / Q000187:drug effects*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D001555:Benzene Derivatives; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D009419:Nerve Tissue Proteins; D016566:Organoselenium Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006151:Guanosine; C061132:diphenyldiselenide; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid