title: Development of pancreatic acinar cell metaplasia after successful administration of omeprazole for 6 months in rats.
abstract: Long-term use of proton pump inhibitors (PPIs) has been reported to worsen corpus atrophic gastritis in patients with Helicobacter pylori infection. On the other hand, PPIs have been associated with fundic gland-type gastric polyps and various histological changes. In the present study, we attempted to establish a protocol for omeprazole (OPZ) administration to rats over a longer period and examined the morphological changes in the gastric mucosa after administration of OPZ for 6 months. A total of 34 Wistar rats (8 weeks old) were used. In a preliminary experiment to determine the appropriate dose of OPZ, the rats had ad libitum access to food containing different doses of OPZ for 1 month. We found an approximate dose of 100 mg/kg body weight/day of OPZ to be most suitable from the point of view of intragastric pH, body weight, and serum gastrin level. In the experiment proper, rats were divided into two groups, either control or OPZ diets, and morphological changes in the gastric mucosa in each group were then examined by hematoxylin and eosin and immunohistochemical staining with alpha-amylase, trypsin, and chromogranin A. Multiple vacuolar degeneration of parietal cells and numerous small mucous cells were evident at 1 month after treatment with OPZ. At 6 months after treatment with OPZ, cystic degeneration and acinar-cell-like cells containing red granules positive for alpha-amylase and trypsin and negative for chromogranin A were detected in the OPZ rats. The serum gastrin level in the OPZ group was significantly higher than that in the control group. We have established a protocol for long-term administration of OPZ in rats that is a useful model for analyzing morphological changes after long-term PPI therapy. Long-term OPZ treatment causes hypergastrinemia and pancreatic acinar cell metaplasia in this animal model.
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Seta-tsukinowa-cho, Ohtsu, Shiga, 520-2192, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mukaisho
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugihara
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D053379:Chromogranin A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005755:Gastrins / Q000097:blood; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D023421:Models, Animal; D009853:Omeprazole / Q000008:administration & dosage / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000201:enzymology; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D000516:alpha-Amylases / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D053379:Chromogranin A; D005755:Gastrins; D054328:Proton Pump Inhibitors; C506153:chromogranin A, rat; D000516:alpha-Amylases; D014357:Trypsin; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole