title: Synergism of Helicobacter pylori infection and stress on the augmentation of gastric mucosal damage and its prevention with alpha-tocopherol.
abstract: Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.
authors.affiliation: Genomic Research Center for Gastroenterology, Ajou University School of Medicine, San 5 Wonchon-dong Yeongtong-gu, Suwon, 443-721, Korea.
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Oh
authors.forename: Marie
authors.initials: M
authors.lastname: Yeo
authors.forename: Sang Uk
authors.initials: SU
authors.lastname: Han
authors.forename: Yong Kwan
authors.initials: YK
authors.lastname: Cho
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Chung
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Ki-Baik
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000166:cytology; D005753:Gastric Mucosa / Q000293:injuries / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013276:Stomach Ulcer / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D024502:alpha-Tocopherol / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D017392:Thiobarbituric Acid Reactive Substances; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D024502:alpha-Tocopherol