谷氨酸能神经传递和氧化应激参与癫痫的病理生理。一些抗惊厥药通过调节这些途径发挥其作用。Trigonelline(TRG)已被证明具有各种药理作用,例如神经保护作用。因此,这项研究是为了确定TRG的抗惊厥作用,关注其对N-甲基-D-天冬氨酸(NMDA)受体的潜在影响,一种谷氨酸受体,PTZ诱导的小鼠癫痫发作中前额叶皮质(PFC)的氧化应激状态。将72只雄性小鼠随机分为9组。这些组包括接受生理盐水的小鼠,剂量为10、50和100mg/kg的TRG,地西泮,NMDA(激动剂),氯胺酮(拮抗剂),TRG与NMDA的有效剂量,以及亚有效剂量的TRG与氯胺酮,分别。所有药物均在PTZ诱导癫痫发作前60分钟腹膜内给药。癫痫发作延迟,总抗氧化能力(TAC),测定血清和PFC中丙二醛(MDA)水平。此外,NR2A和NR2B的基因表达,NMDA受体的亚基,在PFC中测量。TRG给药增加了癫痫发作的潜伏期,并增强了TAC,同时降低了PFC和血清中的MDA水平。TRG也下降了NR2B在PFC中的基因表达。出乎意料的是,研究结果表明,同时服用氯胺酮会放大,而NMDA缓解了,TRG对癫痫发作潜伏期的影响。此外,NMDA降低了TRG对抗氧化能力和氧化应激的积极作用,氯胺酮放大了这些有益的作用,表明TRG和NMDA受体调节之间的复杂相互作用。在NMDA受体的基因表达中,结果表明,氯胺酮与亚有效剂量的TRG共同给药时,NR2B的基因表达显着降低。结果发现,至少部分地,TRG在PTZ诱导的雄性小鼠癫痫发作中的抗惊厥作用是由谷氨酸能神经传递的减弱以及氧化应激的减少介导的。
Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG\'s anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.