Oral malodorous compound activates mitochondrial pathway inducing apoptosis in human gingival fibroblasts

Hydrogen sulfide (H2S) is a main cause of physiologic halitosis. H2S induces apoptosis in human gingival cells, which may play an important role in periodontal pathology. Recently, it has been reported that H2S induced apoptosis and DNA damage in human gingival fibroblasts (HGFs) by increasing the levels of reactive oxygen species. However, the mechanisms of H2S-induced apoptosis have not been clarified in HGFs. The objective of this study was to determine the apoptotic pathway activated by H2S in HGFs. The HGFs were exposed to 50 ng/mL H2S, resulting in 18 ng/mL in the culture medium, which is lower than the concentration in periodontal pockets. The number of apoptotic cells after 24 and 48 h incubation was significantly higher than that in the control cultures (p < 0.05). Mitochondrial membrane depolarization and the release of cytochrome c, and caspase-3, and caspase-9 were also significantly increased after both 24- and 48-h incubation (p < 0.05), whereas caspase-8, a key enzyme in the receptor ligand-mediated pathway causing apoptosis, was not activated. The present study shows that H2S triggered the mitochondrial pathway causing apoptosis in HGFs but did not activate the receptor ligand-mediated pathway.