title: 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.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kanatani
authors.forename: M
authors.initials: M
authors.lastname: Ebata
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D010544:Peroxidases / Q000737:chemistry; D013276:Stomach Ulcer / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D006632:Histamine; D010544:Peroxidases; D009195:Peroxidase; D015232:Dinoprostone; D007213:Indomethacin