Laboratory of Experimental Research in Biological Sciences of Federal University of Piauí, Piauí, Brazil.
Fundam Clin Pharmacol. 2011 Aug;25(4):485-92. doi: 10.1111/j.1472-8206.2010.00862.x. Epub 2010 Jul 15.
This study was aimed at investigating the anticonvulsant activity of lipoic acid (LA) against pilocarpine-induced seizures as well as the effects of this metabolic antioxidant on the hippocampal extracellular concentrations of amino acid neurotransmitters glutamate, aspartate, glycine and glutamate and γ-aminobutyric acid (GABA). In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate concentrations, whereas no significant change was observed in the levels of glycine or GABA. LA (10, 20 or 30 mg/kg) pretreatment completely blocked pilocarpine-evoked increases in extracellular glutamate and aspartate concentrations. Significant reductions in hippocampal GABA and glycine concentrations were also observed although not as pronounced as those shown by glutamate and aspartate. Based on the finding that LA protected rats against pilocarpine-induced seizures, it could be suggested that the reduction in inhibitory amino acid neurotransmitters levels was comparatively minor and offset by a more pronounced reduction in glutamate and aspartate extracellular concentrations. Therefore, the fact that LA could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in rats.
本研究旨在探讨硫辛酸(LA)对匹鲁卡品诱导的癫痫发作的抗惊厥活性,以及这种代谢抗氧化剂对海马细胞外谷氨酸、天冬氨酸、甘氨酸和谷氨酸和γ-氨基丁酸(GABA)等氨基酸神经递质浓度的影响。体内微透析表明,腹腔内给予匹鲁卡品可引起海马谷氨酸和天冬氨酸浓度明显升高,而甘氨酸或 GABA 水平无明显变化。LA(10、20 或 30mg/kg)预处理可完全阻断匹鲁卡品诱导的细胞外谷氨酸和天冬氨酸浓度升高。虽然不像谷氨酸和天冬氨酸那样明显,但也观察到海马 GABA 和甘氨酸浓度显著降低。鉴于 LA 可保护大鼠免受匹鲁卡品诱导的癫痫发作,因此可以认为,抑制性氨基酸神经递质水平的降低相对较小,并且被谷氨酸和天冬氨酸细胞外浓度的更明显降低所抵消。因此,LA 可以明显降低匹鲁卡品诱导的谷氨酸和天冬氨酸增加,这至少部分解释了其在匹鲁卡品诱导的大鼠癫痫发作中的抗惊厥活性。