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

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.