European Surgical Research
Original Paper
Acceleration of Gastric Ulcer Healing by Omeprazole in Portal Hypertensive RatsIs Its Action Mediated by Gastrin Release and the Stimulation of Epithelial Proliferation? Department of Surgery I, Oita Medical University, Oita, Japan
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Article / Publication Details
Received: April 18, 2002
Accepted: August 28, 2002
Published online: April 17, 2003
Issue release date: March – April
Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0
ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)
For additional information: https://www.karger.com/ESR
Abstract
Background: Gastric ulcer healing is delayed in patients with portal hypertension (PHT) and often responds poorly to histamine H2 blockers. Although proton pump inhibitors are more effective anti-ulcer agents, there is little information regarding their efficacy for gastric ulcer in cases of PHT. Therefore, we investigated the effects of a proton pump inhibitor, omeprazole, on the healing of acetic-acid-induced gastric ulcer in PHT rats. Methods: Animals studied were 80 male Sprague-Dawley rats aged 7 weeks, of which half underwent two-staged portal vein ligation (PHT rats) and half underwent a sham operation (SO rats). Gastric ulcers were induced by acetic acid. Starting from day 4 after ulcer induction, rats received omeprazole or vehicle orally (50 mg/kg) for 5 or 10 days. Ulcer area, proliferating cell nuclear antigen labelling index (PCNA LI), and serum gastrin levels were recorded. Results: PHT significantly inhibited epithelial cell proliferation and delayed gastric ulcer healing as indicated by a decreased PCNA LI at the ulcer margin and almost 2-fold larger ulcer area in PHT versus SO rats 14 days after ulcer induction. Ten-day treatment with omeprazole (vs. vehicle) significantly accelerated ulcer healing to a similar extent in both PHT and SO rats. Serum gastrin levels were significantly higher in PHT rats than in SO rats following treatment with omeprazole. Omeprazole (vs. vehicle) restored the decreased PCNA LI at the ulcer margin in PHT rats to that noted in SO rats. Conclusions: In PHT rats, omeprazole accelerates gastric ulcer healing, stimulates epithelial cell proliferation at the ulcer margin, and increases serum gastrin levels. Since gastrin is a potent stimulator of gastric epithelial cell proliferation, increased serum gastrin levels may be an important factor in omeprazole-induced stimulation of epithelial cell proliferation and acceleration of gastric ulcer healing in conditions of PHT.
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References
- Chen LS, Lin HC, Hwang SJ, Lee FY, Hou MC, Lee SD: Prevalence of gastric ulcer in cirrhotic patients and its relation to portal hypertension. J Gastroenterol Hepatol 1996;11:59–64.
- Tsai CJ: Helicobacter pylori infection and peptic ulcer disease in cirrhosis. Dig Dis Sci 1998;43:1219–1225.
- Siringo S, Burroughs AK, Bolondi L, Muia A, Di Febo G, Miglioli M, Cavalli G, Barbara L: Peptic ulcer and its course in cirrhosis: An endoscopic and clinical prospective study. J Hepatol 1995;22:633–641.
- Di Mario F, Gottardello L, Germana B, Dotto P, Grassi SA, Vianello F, Battaglia G, Leandro G, Burra P, Salvagnini M, Naccarato R: Peptic ulcer in cirrhotic patients: A short- and long-term study with antisecretory drugs. Ital J Gastroenterol 1992;24:122–125.
- Walker S, Krishna DR, Klotz U, Bode JC: Frequent non-response to histamine H2-receptor antagonists in cirrhotics. Gut 1989;30:1105–1109.
- Baatar D, Kitano S, Yoshida T, Bandoh T, Ninomiya K, Tsuboi S: Delayed healing of acetic-acid-induced gastric ulcer in portal hypertensive rats. Eur Surg Res 1999;31:340–346.
- Levi S, Goodlad RA, Lee CY, Stamp G, Walport MJ, Wright NA, Hodgson HJF: Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing. Lancet 1990;336:840–843.
- Takeuchi K, Johnson LR: Effect of cell proliferation on healing of gastric and duodenal ulcers in rats. Digestion 1986;33:92–100.
-
Scobie BA, Summerskill WHJ: Reduced gastric acid output in cirrhosis: Quantitation and relationships. Gut 1964;5:422–428.
- Sarfeh IJ, Tarnawski A, Malki A, Mason GR, Mach T, Ivey KJ: Portal hypertension and gastric mucosal injury in rats: Effects of alcohol. Gastroenterology 1983;84:987–993.
- Tsukimi Y, Okabe S: Effect of anterior unilateral vagotomy on healing of kissing gastric ulcers induced in rats. Jpn J Pharmacol 1994;66:105–114.
- Tarnawski A, Stachura J, Krause WJ, Douglass TG, Gergely H: Quality of gastric ulcer healing: A new, emerging concept. J Clin Gastroenterol 1991;13:S42–S47.
-
Kitajima T, Okuhira M, Tani K, Nakano T, Hiramatsu A, Mizuno T, Inoue K: Cell proliferation kinetics in acetic acid-induced gastric ulcer evaluated by immunohistochemical staining of proliferating cell nuclear antigen. J Clin Gastroenterol 1993;17(suppl 1):116–120.
- Celis JE, Celis A: Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: Subdivision of S phase. Proc Natl Acad Sci USA 1985;82:3262–3266.
- Sachs G, Wallmark B: The gastric H+, K+-ATPase: The site of action of omeprazole. Scand J Gastroenterol Suppl 1989;166:3–11.
-
Schmassmann A, Tarnawski A, Peskar BM, Varga L, Flogerzi B, Halter F: Influence of acid and angiogenesis on kinetics of gastric ulcer healing in rats: Interaction with indomethacin. Am J Physiol 1995;268:G276–G285.
- Johnson LR, Guthrie PD: Mucosal DNA synthesis: A short term index of the trophic action of gastrin. Gastroenterology 1974;67:453–459.
- Festen HPM, Thijs JC, Lamers CBHW, Jansen JMBJ, Pals G, Frants RR, Defize J, Meuwissen SGM: Effect of oral omeprazole on serum gastrin and serum pepsinogen I levels. Gastroenterology 1984;87:1030–1034.
- Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Hakanson R: Plasma gastrin and gastric enterochromaffin-like cell activation and proliferation. Gastroenterology 1986;90:391–399.
- Ito M, Segami T, Inaguma K, Suzuki Y: Cimetidine and omeprazole accelerate gastric ulcer healing by an increase in gastric secretion. Eur J Pharmacol 1994;263:253–259.
- Ito M, Segami T, Tsukahara T, Kojima R, Suzuki Y: Effect of cimetidine and omeprazole on gastric ulcer healing of rats with limited food intake time. Eur J Pharmacol 1994;263:245–251.
- Doyle JW, Wolfe M, McGuigan JE: Hepatic clearance of gastrin and cholecystokinin peptides. Gastroenterology 1984;87:60–68.
- van Hoorn-Hickman R, Vinik AI, van Hoorn WA: Transhepatic hormone levels in the portacaval shunted pig: The effects of arginine upon gastrin and glucagon release. Am J Clin Nutr 1979;32:2009–2015.
Article / Publication Details
Received: April 18, 2002
Accepted: August 28, 2002
Published online: April 17, 2003
Issue release date: March – April
Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0
ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)
For additional information: https://www.karger.com/ESR
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