Lesani Ali, Mashaknejadian Behbahani Fatemeh, Manavi Mohammad Amin, Mohammad Jafari Razieh, Shafaroodi Hamed, Khosravi Saman, Dehpour Ahmad Reza
Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacol Rep. 2025 Apr;77(2):450-462. doi: 10.1007/s43440-025-00698-6. Epub 2025 Jan 27.
Epilepsy, a neurological disorder characterized by recurrent seizures, presents considerable difficulties in treatment, particularly when dealing with drug-resistant cases. Dapsone, recognized for its anti-inflammatory properties, holds promise as a potential therapeutic option. However, its effectiveness in epilepsy requires further investigation. The aim of this study is to explore the effects of dapsone on seizure activity and neuroinflammation, particularly through the nuclear factor erythroid-2-related factor (Nrf2)/ Heme Oxygenase 1 (HO-1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathways, to better understand its therapeutic potential.
To evaluate the effects of dapsone, two seizure models were utilized in mice: pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced generalized tonic-clonic seizures (GTCS) in mice. The impact of dapsone on neuroinflammatory markers and oxidative stress pathways, specifically Nrf2/HO-1 and NLRP3, as well as interleukin-1β (IL-1β), IL-8, and IL-18, was assessed using Western blotting and ELISA techniques.
In this study, dapsone (2, 5, 10, and 20 mg/kg, ip) showcased a significant increase in clonic seizure threshold following intravenous infusion of PTZ. Notably, doses of 5, 10, and 20 mg/kg exhibited increased latency and decreased the number of seizures. Additionally, dapsone at 10 and 20 mg/kg prevented the incidence of GTCS and subsequent mortality in the MES model. Furthermore, Dapsone demonstrated modulation of Nrf2/ HO-1 and NLRP3 IL-1 β/IL-18 pathways.
This study highlights the therapeutic potential of dapsone in epilepsy, emphasizing the involvement of Nrf2/HO-1 and NLRP3 pathways. These findings provide a foundation for future clinical research aimed at developing dapsone-based therapies for drug-resistant epilepsy.
癫痫是一种以反复发作性癫痫发作为特征的神经系统疾病，在治疗上存在相当大的困难，尤其是在处理耐药病例时。氨苯砜因其抗炎特性而被认可，有望成为一种潜在的治疗选择。然而，其在癫痫治疗中的有效性需要进一步研究。本研究的目的是探讨氨苯砜对癫痫发作活动和神经炎症的影响，特别是通过核因子红细胞2相关因子（Nrf2）/血红素加氧酶1（HO-1）和NOD样受体家族含pyrin结构域3（NLRP3）途径，以更好地了解其治疗潜力。
为评估氨苯砜的作用，在小鼠中使用了两种癫痫模型：戊四氮（PTZ）诱导的阵挛性癫痫发作和最大电休克（MES）诱导的小鼠全身性强直-阵挛性癫痫发作（GTCS）。使用蛋白质免疫印迹法和酶联免疫吸附测定技术评估氨苯砜对神经炎症标志物和氧化应激途径（特别是Nrf2/HO-1和NLRP3）以及白细胞介素-1β（IL-1β）、IL-8和IL-18的影响。
在本研究中，氨苯砜（2、5、10和20mg/kg，腹腔注射）在静脉注射PTZ后显示阵挛性癫痫发作阈值显著提高。值得注意的是，5、10和20mg/kg剂量表现出潜伏期延长和癫痫发作次数减少。此外，10和20mg/kg的氨苯砜可预防MES模型中GTCS的发生及随后的死亡率。此外，氨苯砜显示出对Nrf2/HO-1和NLRP3 IL-1β/IL-18途径的调节作用。
本研究突出了氨苯砜在癫痫治疗中的潜力，强调了Nrf2/HO-1和NLRP3途径的参与。这些发现为未来旨在开发基于氨苯砜的耐药性癫痫治疗方法的临床研究奠定了基础。
