尼美舒利对大鼠脑匀浆中红藻氨酸诱导的体外氧化损伤的影响。
Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates.
作者信息
Candelario-Jalil Eduardo, Sonia León Olga
机构信息
Department of Pharmacology, University of Havana (CIEB-IFAL), Apartado Postal 6079, Havana City 10600, Cuba.
出版信息
BMC Pharmacol. 2003 Jun 14;3:7. doi: 10.1186/1471-2210-3-7.
BACKGROUND
The cyclooxygenase-2 inhibitor nimesulide is able to reduce kainate-induced oxidative stress in vivo. Here we investigate if this effect is mediated by the direct antioxidant properties of nimesulide using a well-characterized in vitro model of kainate toxicity.
RESULTS
Exposure of rat brain homogenates to kainate (12 mM) caused a significant (p < 0.01) increase in the concentrations of malondialdehyde and 4-hydroxy-alkenals and a significant (p < 0.01) decrease in sulfhydryl levels. High concentrations of nimesulide (0.6-1.6 mM) reduced the extent of lipid peroxidation and the decline in both total and non-protein sulfhydryl levels induced by kainate in a concentration-dependent manner.
CONCLUSIONS
Our results suggest that the neuroprotective effects of nimesulide against kainate-induced oxidative stress in vivo are not mediated through its direct free radical scavenging ability because the concentrations at which nimesulide is able to reduce in vitro kainate excitotoxicity are excessively higher than those attained in plasma after therapeutic doses.
背景
环氧化酶 - 2抑制剂尼美舒利能够在体内减轻海藻酸诱导的氧化应激。在此，我们使用一个特征明确的海藻酸毒性体外模型，研究这种效应是否由尼美舒利的直接抗氧化特性介导。
结果
将大鼠脑匀浆暴露于海藻酸（12 mM）会导致丙二醛和4 - 羟基烯醛浓度显著（p < 0.01）升高，以及巯基水平显著（p < 0.01）降低。高浓度的尼美舒利（0.6 - 1.6 mM）以浓度依赖的方式降低了海藻酸诱导的脂质过氧化程度以及总巯基和非蛋白巯基水平的下降。
结论
我们的结果表明，尼美舒利在体内对海藻酸诱导的氧化应激的神经保护作用并非通过其直接的自由基清除能力介导，因为尼美舒利能够降低体外海藻酸兴奋性毒性的浓度远高于治疗剂量后血浆中所能达到的浓度。
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