Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils.
In this study, we examined the effect of rebamipide, a mucoprotective drug, on gastric ulcer healing in Mongolian gerbils infected with H. pylori. Male Mongolian gerbils were inoculated with H. pylori or vehicle alone 12 hr after the production of an acetic acid-induced gastric ulcer. On day 5, the gerbils inoculated with H. pylori were divided into three groups and fed rebamipide-containing diet (0.038%, 60 mg/kg, or 0.0038%, 6 mg/kg), or standard laboratory chow. The gerbils inoculated with the vehicle were fed standard laboratory chow throughout the experiment. The gerbils were killed on day 5, 15, or 30 after ulcer production, and removed stomachs were subjected to calculation of ulcer size, culture for H. pylori, and measurement of myeloperoxidase activity, a marker for neutrophil infiltration, in ulcerated tissue. Apoptotic and proliferating cells of gastric epithelium in ulcer margins were detected by the in situ DNA nick end-labeling method and immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU), respectively. Rebamipide did not affect colonization levels of H. pylori. Infection with H. pylori did not affect ulcer size by day 5 but significantly delayed ulcer healing by days 15 and 30, accompanied by an increase in the number of apoptotic cells, a decrease in the number of BrdU-positive cells, and an increase in myeloperoxydase activity. Rebamipide prevented delay of ulcer healing and abolished these effects of H. pylori on cell kinetics and neutrophil infiltration. In conclusion, rebamipide may prevent the delay of acetic acid-induced gastric ulcer healing caused by H. pylori through modulating cell kinetics and inhibiting neutrophil infiltration.
Department of Gastroenterology, Osaka City University Medical School, Japan.
Toshio
T
Watanabe
Kazuhide
K
Higuchi
Masaki
M
Hamaguchi
Tetsuya
T
Tanigawa
Rikimon
R
Wada
Kazunari
K
Tominaga
Yasuhiro
Y
Fujiwara
Tetsuo
T
Arakawa
D019342:Acetic Acid / Q000009:adverse effects; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division; D004848:Epithelium; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D008297:Male; D020556:Neutrophil Infiltration; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000382:microbiology*; D014945:Wound Healing
D000897:Anti-Ulcer Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine; D019342:Acetic Acid