title: [Pharmacological study on the pathological changes of the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils].
abstract: Helicobacter pylori (H. pylori) infection has been recognized to be a causal factor of gastritis, ulcers and gastric cancer in man. Using Mongolian gerbils (M. gerbils), which are suitable for an H. pylori infection animal model, we examined 1) how H. pylori infection, indomethacin and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed acetic acid ulcers; and 2) whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes, including gastric adenocarcinoma. 1) H. pylori infection significantly delayed ulcer healing 4 weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected M. gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from 1 to 6 months after infection, with a gradual increase in size. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. 2) Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole + clarithromycin. Immediately after treatment ended in both the 5 and 9 month groups, it was verified that H. pylori were completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible; and atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the non-treated control group. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that 1) H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse; and 2) early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in M gerbils.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Keto
authors.forename: M
authors.initials: M
authors.lastname: Ebata
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology / Q000517:prevention & control; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori; D007213:Indomethacin / Q000009:adverse effects; D009853:Omeprazole / Q000627:therapeutic use; D012008:Recurrence; D013274:Stomach Neoplasms / Q000382:microbiology / Q000517:prevention & control; D013276:Stomach Ulcer / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D017291:Clarithromycin; D009853:Omeprazole; D007213:Indomethacin