The protective of hydrogen on stress-induced gastric ulceration

Int Immunopharmacol. 2012 Jun;13(2):197-203. doi: 10.1016/j.intimp.2012.04.004. Epub 2012 Apr 24.


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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cold Temperature / adverse effects
  • Cytokines / genetics
  • Free Radical Scavengers / pharmacology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / injuries
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gene Expression / drug effects
  • Hydrogen / administration & dosage
  • Hydrogen / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Restraint, Physical / adverse effects
  • Stomach Ulcer / etiology
  • Stomach Ulcer / metabolism
  • Stomach Ulcer / pathology
  • Stomach Ulcer / prevention & control*
  • Stress, Physiological


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Cytokines
  • Free Radical Scavengers
  • RNA, Messenger
  • Reactive Oxygen Species
  • Hydrogen