A novel carbazole-based hydrogen-sulfide donor suppresses seizures and upregulates ATP-sensitive potassium channels

Epilepsy is characterized by repeated spontaneous seizures and remains untreatable due to its complicate pathogenesis. Low-dose hydrogen sulfide (H 2 S) has been shown to exert antiepileptic and protective effects in the central nervous system, but the administration of H 2 S gas to suppress seizures is difficult. In the present study, we synthesized a safe and efficient carbazole-based H 2 S donor from aldehydes with a one-pot procedure and characterized this specific H 2 S donor via proton nuclear magnetic resonance ( 1 HNMR), scanning electron microscopy (SEM), and absorption spectroscopy. In vitro and in vivo risk assessments demonstrated that the H 2 S donor (up to a 400-μM concentration) had sufficient biocompatibility and membrane permeability and suppressed epileptic seizures. Importantly, the suppression of seizures was determined in the brain when the H 2 S donor was injected into the lateral ventricle in a rat model of advanced seizures. Furthermore, the mechanism by which the H 2 S donor suppressed the expression of seizures may have been related to H 2 S donor-induced increases in the expressions of the ATP-sensitive potassium channel (K ATP ) subunits, Kir6.2 and SUR1. Taken together, these assays suggested that our novel H 2 S donor may represent a potential therapeutic strategy for ameliorating seizures in epilepsy.