Oxidative stress, inflammation and pyroptosis are three of the most important mechanisms in the pathophysiology of temporal lobe epilepsy (TLE). Most people with TLE are refractory to the existing drugs. Sinomenine has shown neuroprotective effects through counteracting oxidative stress, inflammation and pyroptosis. In this study, we evaluated the effect of sinomenine on seizure behavior, oxidative stress, inflammation and pyroptosis markers in addition to its neuroprotective potential in intrahippocampal kainate-induced rat model of TLE. For this purpose, male rats (n = 60) were randomly divided into five groups, i.e., sham, kainate (lesion) with an intrahippocampal injection of kainate, kainate groups receiving sinomenine at doses of 30 or 50 mg/kg, and kainate group receiving valproic acid at a dose of 200 mg/kg (as the positive control). Our obtained data showed that sinomenine administration at a dose of 50 mg/kg can significantly decreases severity of seizures and incidence of status epilepticus (SE), hippocampal aberrant MFS and DNA fragmentation and prevents reduction of neuronal density. It also significantly restored level of ROS, MDA, HO-1 and SOD but its effect on GSH level was not significant. Additionally, sinomenine at a dose of 50 mg/kg partially counteracted the increase of NF-κB, TLR 4, TNFα, GFAP and caspase 1. These results suggest that sinomenine has anticonvulsant and neuroprotective effects by reducing hippocampal oxidative stress, inflammation, pyroptosis and apoptosis in intrahippocampal kainate model of TLE.

中文翻译：

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青藤碱对颞叶癫痫海人酸大鼠模型的神经保护和抗惊厥作用：氧化应激、炎症和细胞焦亡的参与

氧化应激、炎症和细胞焦亡是颞叶癫痫 (TLE) 病理生理学中最重要的三种机制。大多数 TLE 患者对现有药物无效。青藤碱通过对抗氧化应激、炎症和细胞焦亡显示出神经保护作用。在这项研究中，我们评估了青藤碱在海马内红藻氨酸诱导的 TLE 大鼠模型中，除了其神经保护潜力外，还对癫痫发作行为、氧化应激、炎症和细胞焦亡标志物的影响。为此，将雄性大鼠（n = 60）随机分为五组，即假手术组、海马酸海马酸（损伤）组、海马酸海马酸组、青藤碱剂量为 30 或 50 mg/kg 的红藻酸组和海人酸组接受剂量为 200 mg/kg 的丙戊酸（作为阳性对照）。我们获得的数据显示，青藤碱以 50 mg/kg 的剂量给药可显着降低癫痫发作的严重程度和癫痫持续状态 (SE)、海马异常 MFS 和 DNA 断裂的发生率，并防止神经元密度降低。它还显着恢复了 ROS、MDA、HO-1 和 SOD 的水平，但对 GSH 水平的影响不显着。此外，50 mg/kg 剂量的青藤碱部分抵消了 NF-κB、TLR 4、TNFα、GFAP 和 caspase 1 的增加。这些结果表明青藤碱通过减少海马氧化应激、炎症、细胞焦亡和细胞焦亡具有抗惊厥和神经保护作用。 TLE海马内红藻氨酸模型中的细胞凋亡。