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Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori
  1. Tadashi Hagiwara,
  2. Ken-ichi Mukaisho,
  3. Takahisa Nakayama,
  4. Hiroyuki Sugihara,
  5. Takanori Hattori
  1. Department of Pathology, Shiga University of Medical Science, Shiga, Japan
  1. Correspondence to Dr K Mukaisho, Department of Pathology, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga 520-2192, Japan; mukaisho{at}


Background We investigated whether corpus atrophic gastritis worsens in Mongolian gerbils (MGs) after long-term administration of proton pump inhibitor (PPI). MGs are an excellent model for studying Helicobacter pylori-related gastritis and adenocarcinoma.

Methods MGs were separated into four groups (n =15/group); H pylori (ATCC43504) was inoculated into the OPZ(omeprazole)+Hp (H pylori) and Hp groups, a PPI (OPZ) was administered to the OPZ+Hp and OPZ groups and the control group received no treatment. MGs had access to food containing omeprazole (100 mg/kg body weight/day) for 6 months, after which their stomachs were removed and cut into nine sections (six sections in the fundus and three sections in the antrum). Corpus atrophy was evaluated by the absence of parietal cells in the six sections in the fundus. First, we calculated a percentage of the area devoid of parietal cells in each haematoxylin and eosin-stained section, and then we scored the degree of atrophy by adding the percentages of the six sections. A full score was 600.

Results Neutrophilic and lymphoid infiltrates were greater in the OPZ+Hp group than in the other groups. The corpus atrophy score in the OPZ+Hp group was significantly higher than that in the Hp group (p<0.0048, Student t test). Significantly more adenocarcinomas were found in the OPZ+Hp (60%) than in the Hp (7%) group animals.

Conclusion Long-term PPI administration promotes development of adenocarcinoma, which is associated with the progression of atrophic corpus gastritis in MGs infected with H pylori.

  • PPI
  • adenocarcinoma
  • Helicobacter pylori, Mongolian gerbils
  • long-term
  • gastrin
  • gastritis
  • proton pump inhibition

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  • See Commentary, p 567

  • Linked articles 229286.

  • Competing interests None.

  • Ethics approval All procedures complied with the ethical guidelines for animal experimentation and the care and use of laboratory animals at Shiga University of Medical Science, Japan.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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