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Cooperation of Non-Effective Concentration of Glutamatergic System Modulators and Antioxidant Against Oxidative Stress Induced by Quinolinic Acid

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Abstract

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.

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Acknowledgments

This work was supported by the FINEP research grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)” # 01.06.0842-00, INCT for Excitotoxicity and Neuroprotection-MCT/CNPq. J.B.T.R and F.A.A.S. receive a fellowship by CNPq. F.D. and C.L.D.C. receive a fellowship by CAPES. Additional support giving by FAPERGS and CAPES. This work was revised by BioMed Proofreading.

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  1. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, CEP 97105-900, Brazil

    Fernando Dobrachinski, Luiza Lena Bastos, Jessika Cristina Bridi, Cristiane Lenz Dalla Corte, João Batista Teixeira da Rocha & Félix Alexandre Antunes Soares

  2. Departamento de Ciências da Saúde, Universidade Federal do Pampa, Campus Uruguaiana, Uruguaiana, RS, Brazil

    Daiana Silva de Ávila

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  1. Fernando Dobrachinski
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Correspondence to Félix Alexandre Antunes Soares.

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Dobrachinski, F., Bastos, L.L., Bridi, J.C. et al. Cooperation of Non-Effective Concentration of Glutamatergic System Modulators and Antioxidant Against Oxidative Stress Induced by Quinolinic Acid. Neurochem Res 37, 1993–2003 (2012). https://doi.org/10.1007/s11064-012-0820-3

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