Stress ulceration frequently occurs as a result of major stressful events and hydroxyl radical (⋅OH) is one of the major causative factors for it.

Recently, it has been proved that hydrogen, a potent selectively ⋅OH scavenger, can effectively protect animals against ROS-induced tissue damage.

In like manner, we hypothesize that hydrogen may have a protective effect against stress ulceration.

Gastric ulceration was induced by the method of cold restraint stress.

Rats in the hydrogen treatment group received hydrogen-rich saline (10 mL/kg body weight) 5 min before the stress.

At 6h post-stress, gastric corpus mucosa was harvested for the measurement of malondialdehyde, protein carbonyl, 8-hydroxy-desoxyguanosine, glutathione, superoxide dismutase, myeloperoxidase, TNF-α, IL-1β and cytokine-induced neutrophils chemoattractant-1.

In addition, western blotting was used to determine the expression of p38 MAPK, P-p38 MAPK, P-JNk, JNK, Bcl-xl, Bax and cleaved caspase-3.

Nuclear translocation of NF-κB was assessed by electrophoretic mobility shift assay.

Gastric mucosa structure and mucosal epithelial cells apoptosis were measured at 12h post-stress.

Our present study showed that hydrogen treatment lessened the stress-induced lipid peroxidation, protein carbonyl and DNA oxidant and improved tissue antioxidant potential.

In addition, hydrogen mitigated inflammatory response and neutrophils infiltration with suppressing the activity of P-p38 MAPK, P-JNk and NF-κB.

Importantly, hydrogen ameliorated gastric mucosa damage with preventing cell apoptosis.

Furthermore, the up-regulation of cleaved caspase-3, Bax and down-regulation of Bcl-xl expression were blocked by hydrogen treatment.

In conclusion, hydrogen treatment effectively ameliorated stress-associated gastric mucosa damage via its anti-oxidant, anti-inflammatory and anti-apoptotic effects.