Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, S.S.A., Ave. Insurgentes Sur, No. 3877, C.P. 14269, Mexico, DF, Mexico.
Neurochem Res. 2013 Sep;38(9):1819-27. doi: 10.1007/s11064-013-1087-z. Epub 2013 Jun 1.
Excitotoxicity due to glutamate receptors (GluRs) overactivation is a leading mechanism of oxidative damage and neuronal death in various diseases. We have shown that dapsone (DDS) was able to reduce both neurotoxicity and seizures associated to the administration of kainic acid (KA), an agonist acting on AMPA/KA receptors (GluK1-GluK5). Recently, it has been shown that phenobarbital (PB) is also able to reduce epileptic activity evoked by that receptor. In the present study, we tested the antioxidative, anticonvulsive and neuroprotective effects of DDS and PB administered alone or in combination upon KA toxicity to rats. Results showed that KA increased lipid peroxidation and diminished reduced glutathione (GSH), 24 h after KA administration and both drugs in combination or individually inhibited these events. Likewise, KA promotes mortality and this event was antagonized by effect of both treatments. Additionally, the behavioral evaluation showed that DDS and PB administered alone or in combination decreased the number of limbic seizures and reduced the percentage of animals showing tonic-clonic seizures versus the control group, which was administered only with KA. Finally, our study demonstrated that all of the treatments prevented the neuronal death of the pyramidal cell layer of hippocampal CA-3. In conclusion, the treatment with DDS and PB administrated alone or in combination exerted antioxidant, anticonvulsive and neuroprotective effects against the neurotoxicity induced by KA in rats, but their effects were not additive. Thus, it may be good options of treatment in diseases such as epilepsy and status epilepicus, administered separately.
谷氨酸受体（GluRs）过度激活导致的兴奋毒性是各种疾病中氧化损伤和神经元死亡的主要机制。我们已经表明，氨苯砜（DDS）能够降低与作为 AMPA/KA 受体（GluK1-GluK5）激动剂的海人酸（KA）给药相关的神经毒性和癫痫发作。最近，已经表明苯巴比妥（PB）也能够降低该受体诱发的癫痫活性。在本研究中，我们测试了 DDS 和 PB 单独或联合给药对 KA 毒性的抗氧化、抗惊厥和神经保护作用。结果表明，KA 增加了脂质过氧化作用，减少了还原型谷胱甘肽（GSH），在 KA 给药后 24 小时，这两种药物单独或联合使用均可抑制这些事件。同样，KA 促进了死亡率，这一事件被两种治疗方法的效果拮抗。此外，行为评估表明，DDS 和 PB 单独或联合给药减少了边缘性癫痫发作的次数，并降低了与对照组相比出现强直-阵挛性癫痫发作的动物百分比，对照组仅给予 KA。最后，我们的研究表明，所有治疗都防止了海马 CA-3 锥体细胞层的神经元死亡。总之，DDS 和 PB 单独或联合给药对 KA 诱导的大鼠神经毒性具有抗氧化、抗惊厥和神经保护作用，但它们的作用不是相加的。因此，在癫痫和癫痫持续状态等疾病中，单独使用这些药物可能是一种很好的治疗选择。
