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Effects of indomethacin and rofecoxib on gastric mucosal damage in normal and Helicobacter pylori-infected mongolian gerbils.

Abstract
This study examined the effects of indomethacin and rofecoxib on normal and Helicobacter pylori (H. pylori)-infected gastric mucosa of Mongolian (M.) gerbils. M. gerbils (6-wk-old) were orally administered H. pylori (ATCC43504, 2 x 10(8) CFU/ml) after fasting for 24 hours. Beginning 3 mo after inoculation, indomethacin (2 mg/kg, s.c) or rofecoxib (10 mg/kg, p.o.) was administered once daily for 2 wk to the gerbils. At autopsy, gastric mucosal ulcer area, myeroperoxidase (MPO) activity, prostaglandin (PG) E(2) synthesis, and H. pylori viability were determined. Histamine-stimulated gastric acid secretion was measured with the acute gastric fistula method. Histological study was performed with H&E staining. H. pylori infection caused severe mucosal damage and production of lymphoid follicles in the gastric submucosa. In H. pylori-infected gerbils, indomethacin aggravated the gastric mucosal damage induced by H. pylori infection. Furthermore, indomethacin by itself induced gastric ulcers at an incidence of 6/10. In contrast, rofecoxib did not aggravate the H. pylori-induced mucosal damage. Indomethacin and rofeocoxib significantly reduced H. pylori viability. MPO activity was significantly increased in H. pylori-infected gerbils compared with H. pylori-uninfected gerbils. Indomethacin and rofecoxib reduced MPO activity in H. pylori-infected gerbils. PGE(2) synthesis was markedly increased in H. pylori-infected gerbils (approximately 3-times) compared with the normal gerbils. Indomethacin significantly inhibited PGE(2) synthesis in the gastric mucosa, both in normal and H. pylori-infected gerbils. Rofecoxib did not reduce PGE(2) synthesis in normal gerbils, however, PGE(2) synthesis was reduced to normal levels in H. pylori-infected gerbils. In H. pylori-infected gerbils, histamine-stimulated gastric acid secretion was reduced compared with normal gerbils. Indomethacin significantly increased histamine-stimulated gastric acid secretion and rofecoxib tended to increase secretion in H. pylori-infected gerbils. It was concluded that indomethacin enhances development of gastric mucosal damage in normal gerbils and aggravates H. pylori-induced gastric damage, resulting in gastric ulcers. Rofecoxib did not induce gastric damage in normal gerbils and did not aggravate damage in H. pylori-infected gerbils, suggesting that rofecoxib is less damaging to the stomach than indomethacin.
AuthorsK Kanatani, M Ebata, M Murakami, S Okabe
JournalJournal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 55 Issue 1 Pt 2 Pg. 207-22 (Mar 2004) ISSN: 0867-5910 [Print] Poland
PMID15082879 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Lactones
  • Sulfones
  • rofecoxib
  • Histamine
  • Peroxidases
  • Peroxidase
  • Dinoprostone
  • Indomethacin
Topics
  • Administration, Oral
  • Animals
  • Dinoprostone (antagonists & inhibitors, metabolism)
  • Drug Administration Schedule
  • Drug Synergism
  • Gastric Acid (metabolism)
  • Gastric Mucosa (drug effects, metabolism, pathology)
  • Gerbillinae
  • Helicobacter Infections (drug therapy, metabolism, physiopathology)
  • Helicobacter pylori (isolation & purification)
  • Histamine (pharmacology)
  • Indomethacin (adverse effects, pharmacology, therapeutic use)
  • Injections, Subcutaneous
  • Lactones (pharmacology)
  • Male
  • Peroxidase (drug effects, metabolism)
  • Peroxidases (chemistry)
  • Stomach Ulcer (microbiology, pathology, physiopathology)
  • Sulfones (pharmacology)
  • Time Factors

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