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KMID : 1031120220120020039
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Journal of Epilepsy Research
2022 Volume.12 No. 2 p.39 ~ p.47
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Dapsone Protects Against Lithium-Pilocarpine-Induced Status Epilepticus in Rats through Targeting Tumor Necrosis Factor-α and Nitrergic Pathway
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Koohfar Amirhossein
Eslami Faezeh
Shayan Maryam
Rahimi Nastaran
Moradi Farid
Golroudbari Hasti Tashak
Ghasemi Mehdi
Dehpour Ahmad Reza
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Abstract
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Background and Purpose: Status epilepticus (SE) results in permanent neuronal brain damage in the central nervous system. One of the complex etiologies underlying SE pathogenesis is neuroinflammation. Dapsone has been recently considered as a potential neuroprotective agent in neuroinflammatory conditions. Therefore, the present study aims to investigate effects of dapsone on lithium-pilocarpine-induced SE in rats and assess whether tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) pathway participate in this effect.
Methods: SE was established by injecting lithium chloride (127 mg/kg, intraperitoneally [i.p.]) and pilocarpine (60 mg/kg, i.p.). The animals received pre-treatment dapsone (2, 5, 10, and 20 mg/kg, oral gavage) and post-treatment dapsone (10 mg/kg). Subsequently, seizure score and mortality rate were documented. To assess the underlying signaling pathway, L-Nω-Nitro-L-arginine methyl ester hydrochloride (a non-specific NO synthase [NOS] inhibitor), 7-nitroindazole (a specific neuronal NOS inhibitor), and aminoguanidine (a specific inducible NOS inhibitor) were administered 15 minutes before dapsone (10 mg/kg) pre- or post-treatment. Hippocampal tissue TNF-α and NO concentrations were quantified using the enzyme-linked immunosorbent assay method.
Results: Dapsone (10 mg/kg) pre-and post-treatment significantly attenuated the increased seizure score and mortality rate due to lithium-pilocarpine-induced SE. The development of SE in animals was associated with higher TNF-α and NO metabolites levels, which notably decreased in the dapsone-treated rats. Moreover, co-administration of NOS inhibitors with dapsone markedly reversed the anti-epileptic effects of dapsone and caused an escalation in TNF-α level but a significant reduction in NO concentration level.
Conclusions: It seems that dapsone may exert an anti-epileptic effect on lithium-pilocarpine-induced SE through TNF-α inhibition and modulation of the nitrergic pathway.
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KEYWORD
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Dapsone, Status epilepticus, Nitric oxide, Tumor necrosis factor-alpha
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