Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS CEP 97105-900, Brazil.
Neurochem Res. 2012 Sep;37(9):1993-2003. doi: 10.1007/s11064-012-0820-3. Epub 2012 Jun 7.
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.
过量的活性氧（ROS）形成和谷氨酸摄取的破坏被认为是导致喹啉酸（QA）诱导毒性的关键机制。因此，我们在这里研究二苯基二硒醚（PhSe）（2）、鸟苷（GUO）和 MK-801 的单独或联合使用是否可以保护大鼠脑片免受 QA 诱导的毒性。QA（1 mM）在暴露 2 小时后增加 ROS 形成、硫代巴比妥酸反应性物质（TBARS）和降低细胞活力。（PhSe）（2）（1 μM）在皮质和纹状体中可防止这种 ROS 形成，并可防止 QA 诱导的细胞活力下降。（PhSe）（2）（5 μM）可防止海马体中 ROS 的形成。GUO（10 和 100 μM）可阻止 QA 引起的 ROS 形成增加，而 MK-801（20 和 100 μM）则消除了 QA 的促氧化作用。当使用无效浓度联合使用时，ROS 形成减少，主要是（PhSe）（2）+GUO 和（PhSe）（2）+GUO+MK-801。这些结果表明，这种组合可能有效避免高浓度 QA 引起的毒性作用。此外，在 ROS 形成和细胞活力测定中获得的数据表明，在神经退行性过程中存在不同的途径来改善 QA 毒性。
