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

Abstract

Epilepsy is characterized by repeated spontaneous seizures and remains untreatable due to its complicate pathogenesis. Low-dose hydrogen sulfide (H2S) has been shown to exert antiepileptic and protective effects in the central nervous system, but the administration of H2S gas to suppress seizures is difficult. In the present study, we synthesized a safe and efficient carbazole-based H2S donor from aldehydes with a one-pot procedure and characterized this specific H2S donor via proton nuclear magnetic resonance (1HNMR), scanning electron microscopy (SEM), and absorption spectroscopy. In vitro and in vivo risk assessments demonstrated that the H2S 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 H2S donor was injected into the lateral ventricle in a rat model of advanced seizures. Furthermore, the mechanism by which the H2S donor suppressed the expression of seizures may have been related to H2S donor-induced increases in the expressions of the ATP-sensitive potassium channel (KATP) subunits, Kir6.2 and SUR1. Taken together, these assays suggested that our novel H2S donor may represent a potential therapeutic strategy for ameliorating seizures in epilepsy.