Acute anticonvulsant effects of dapsone on PTZ- and MES-induced seizures in mice: NLRP3 inflammasome inhibition and Nrf2/HO-1 pathway preservation.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pharmacological Reports Pub Date : 2025-04-01 Epub Date: 2025-01-27 DOI:10.1007/s43440-025-00698-6

Ali Lesani, Fatemeh Mashaknejadian Behbahani, Mohammad Amin Manavi, Razieh Mohammad Jafari, Hamed Shafaroodi, Saman Khosravi, Ahmad Reza Dehpour

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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氨苯砜对PTZ和mes诱导小鼠癫痫发作的急性抗惊厥作用：NLRP3炎性小体抑制和Nrf2/HO-1通路保存

背景：癫痫是一种以反复发作为特征的神经系统疾病，在治疗方面存在相当大的困难，特别是在处理耐药病例时。氨苯砜因其抗炎特性而被公认，有望成为一种潜在的治疗选择。然而，其治疗癫痫的有效性有待进一步研究。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pyrin结构域- 3 （NLRP3）途径，以更好地了解其治疗潜力。方法：采用戊四唑（PTZ）致小鼠阵挛性发作模型和最大电休克（MES）致小鼠全身性强直-阵挛性发作（GTCS）模型评价氨苯砜的作用。采用Western blotting和ELISA技术评估氨苯砜对神经炎症标志物和氧化应激通路的影响，特别是Nrf2/HO-1和NLRP3，以及白细胞介素-1β (IL-1β)、IL-8和IL-18。结果：在本研究中，静脉输注PTZ后，氨苯砜（2、5、10和20 mg/kg， ip）显着增加了慢性癫痫发作阈值。值得注意的是，5、10和20 mg/kg剂量增加了潜伏期，减少了癫痫发作次数。此外，在MES模型中，10和20 mg/kg的氨苯砜可以预防GTCS的发生和随后的死亡率。此外，氨苯砜还能调节Nrf2/ HO-1和NLRP3的IL-1 β/IL-18通路。结论：本研究强调了氨苯砜在癫痫中的治疗潜力，强调了Nrf2/HO-1和NLRP3通路的参与。这些发现为未来的临床研究提供了基础，旨在开发以氨砜为基础的治疗耐药癫痫的方法。

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来源期刊

Pharmacological Reports 医学-药学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.