Dapsone Protects Against Lithium-Pilocarpine-Induced Status Epilepticus in Rats through Targeting Tumor Necrosis Factor-α and Nitrergic Pathway.

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-N-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.