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.