A hydrogen sulfide donor suppresses pentylenetetrazol-induced seizures in rats via PKC signaling.

ABSTRACT

Epilepsy is a serious neurological disorder. Available antiepileptic drugs are still lacking. Hydrogen sulfide (H2S), a neuron-protective endogenous gasotransmitter, is reported to have effect on epilepsy. But it remains to be determined for its mechanism. In the present study, we found that a novel carbazole-based H2S donor could effectively suppress pentylenetetrazol-induced seizures in rats. The H2S donor could alleviate not only the epileptic behavior of animals but also the hippocampal EEG activity of seizures. The H2S donor down-regulated the expression of aquaporin 4 in the hippocampus of epilepsy rats. The H2S donor also decreased the seizure-induced release of inflammatory cytokines including IL-1ß, IL-6 and TNF-α. In addition, the H2S donor increased protein kinase C (PKC) expression in the hippocampus of epilepsy rats. These effects of the H2S donor on epilepsy rats were attenuated after blockade of PKC signaling by Go6983, suggesting that PKC signaling participated in the antiepileptic process of H2S donor. Taken together, the H2S donor has a beneficial effect on epilepsy control in a PKC-dependent manner.