Associação do disseleneto de difenila e moduladores do sistema glutamatérgico frente ao dano oxidativo causado por ácido quinolínico

• Autor(a) principal: Dobrachinski, Fernando
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações do UFSM
• Texto Completo: http://repositorio.ufsm.br/handle/1/11214
• topic: Composto orgânico de selênio; Guanosina; MK-801; Sistema glutamatérgico; Ácido quinolínico; Estresse oxidativo; Organoselenium compound; Guanosine; MK-801; Glutamatergic system; Quinolinic acid; Oxidative stress; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA

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 non effective 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.