A protective role of hydrogen sulfide against oxidative stress in rat gastric mucosal epithelium

We investigated effect of hydrogen sulfide (H2S) on oxidative stress-caused cell death in gastric mucosal epithelial cells. In rat normal gastric epithelial RGM1 cells, NaHS, a H2S donor, at 1.5 mM strongly suppressed hydrogen peroxide (H2O2)-caused cell death, while it slightly augmented the H2O2 toxicity at 0.5–1 mM. The protective effect of NaHS was abolished by inhibitors of MEK or JNK, but not of p38 MAP kinase. NaHS at 1.5 mM actually phosphorylated ERK and JNK in RGM1 cells. Glibenclamide, an ATP-sensitive K+ (KATP+) channel inhibitor, did not affect the protective effect of NaHS, although mRNAs for KATP+ channel subunits, Kir6.1 and SUR1, were detected in RGM1 cells. In anesthetized rats, oral administration of NaHS protected against gastric mucosal lesion caused by ischemia-reperfusion. These results suggest that NaHS/H2S may protect gastric mucosal epithelial cells against oxidative stress through stimulation of MAP kinase pathways, a therapeutic dose range being very narrow.