Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

癫痫持续状态 (SE) 是最严重的癫痫形式，会导致脑损伤。导致癫痫病理生理学和神经元死亡的机制仍然存在不确定性。最近，细胞内铁离子超载被确定为一种新认​​识的受控细胞死亡形式（称为铁死亡）的原因。根据最近的研究，抑制铁死亡已显示出作为癫痫治疗的前景。因此，本研究旨在评估 CoQ10 单独使用或与标准抗癫痫药物丙戊酸钠 (SVP) 联合使用可能产生的抗癫痫作用，并评估 COQ10 对 SE 大鼠模型中海马氧化应激和铁死亡的靶向作用。使用锂-毛果芸香碱大鼠癫痫模型，我们评估了 SVP、CoQ10 或两者对海马癫痫发作严重程度、组织学和免疫组织化学的影响。此外，由于氧化应激和脂质过氧化在诱导铁死亡中的重要作用，我们评估了组织匀浆中的丙二醛 (MDA)、还原型谷胱甘肽 (GSH)、谷胱甘肽过氧化物酶 4 (GPX4) 和铁蛋白。我们的工作表明，铁死亡发生在锂-毛果芸香碱诱发癫痫发作的小鼠模型（癫痫组）中。尼氏染色显示显着的神经变性。在海马体中观察到用星形胶质细胞特异性标记物染色的星形胶质细胞数量显着增加。与 SVP 相比，单独施用 CoQ10 可以在癫痫模型中有效缓解癫痫发作。这是通过降低海马组织匀浆中的铁蛋白水平、增加 GPX4、减少 MDA 和增加 GSH 来实现的。此外，与单独使用 SVP 相比，通过加入 CoQ10，SVP 疗法在调节铁储备、GPX4 和氧化应激标记物方面的益处得到了放大。结论：单独使用CoQ10比单独使用SVP在恢复组织学结构方面具有更有利的作用，并且对海马氧化应激和铁死亡有针对性的作用。此外，COQ10 可用作 SVP 的佐剂，以防止癫痫发作引起的氧化损伤和铁死亡相关损伤。