Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.

中文翻译：

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地拉罗司通过调节 ITPRIP 改善脑铁稳态来发挥抗癫痫作用

癫痫是一个全球性的健康问题，影响着数百万人，大约三分之一的患者表现出耐药性。最近的研究揭示了癫痫患者和动物模型中脑铁含量的变化。然而，现有文献缺乏对调节铁稳态作为癫痫干预措施的影响的全面探索。这项研究调查了地拉罗司（一种铁离子螯合剂）对癫痫的影响。这项研究明确证实了地拉罗司在红藻氨酸诱导的癫痫模型中的抗癫痫功效。此外，地拉罗司给药可减轻戊四唑诱导的点燃模型中的癫痫易感性。相反，通过补充剂增加铁水平已成为诱发癫痫发作的潜在加剧因素。有趣的是，我们的调查揭示了一个迄今为止未报道的发现：ITPRIP 被确定为兴奋性突触传递的关键调节剂，调节地拉罗司治疗反应中的癫痫发作。总之，我们的研究结果表明，地拉罗司通过精确靶向 ITPRIP 和改善脑铁稳态来发挥其抗癫痫作用，表明地拉罗司是一种有前景的新型癫痫干预治疗途径。