Hydrogen Sulfide and Carbon Monoxide Are in Synergy with Each Other in the Pathogenesis of Recurrent Febrile Seizures

Abstract
The purpose of the present study was to investigate the interaction between hydrogen sulfide (H2S) and carbon monoxide (CO) during recurrent febrile seizures (FS) H2S and CO are important intra- and intercellular messengers, regulating various brain functions. Our recent studies showed that both of them alleviate the hippocampal damage induced by recurrent FS. In the present study, on a rat model of recurrent FS, we found that hydroxylamine (an inhibitor of cystathionine b-synthase, CBS) reduced CO level and downregulated heme oxygenase (HO-1) expression, while NaHS (a donor of H2S) elevated CO level and upregulated HO-1 expression. ZnPP-IX (an inhibitor of HO-1) decreased H2S formation and downregulated CBS expression, while hemin (which increases the production of endogenous CO) enhanced H2S formation and elevated CBS expression. Our data demonstrate that endogenous H2S and CO are in synergy with each other in recurrent FS.