Effects of cyclooxygenase-2 inhibitor on gastric acid secretion in Helicobacter pylori-infected C57BL/6 mice.
BACKGROUND
Helicobacter pylori-associated body gastritis inhibits gastric acid secretion. The aim of this study was to determine the effects of H. pylori infection on gastric acid secretion and further determine whether cyclooxygenase-2 was involved.


METHODS
C57BL/6 mice (n = 40) were inoculated with the Sydney strain of H. pylori. Control mice (n = 40) were treated with vehicle only. Half of the infected and control mice were fed an experimental diet containing etodolac (10 mg/kg/day) from 1 week after inoculation until the end of the experiment. Before, 12 and 24 weeks after inoculation, the gastric acid secretion, prostaglandin E2 (PGE2) levels in the gastric mucosa, and gastritis scores according to the updated Sydney system were determined. Immunohistochemical staining of COX-2 protein was also performed.


RESULTS
No significant changes in gastric acid secretion, gastritis scores or PGE2 levels in the gastric mucosa were observed in uninfected groups with or without etodolac treatment during the study period. In the H. pylori-infected group without etodolac treatment, gastric acid secretion was significantly decreased with increases in PGE2 levels in the gastric mucosa 24 weeks after inoculation compared with the controls. Gastritis score for activity was significantly higher, and strong staining for COX-2 protein was observed in the H. pylori-infected group. In the H. pylori-infected group with etodolac treatment, PGE2 in the gastric mucosa was decreased and acid secretion was restored to the same level as in the control group.


CONCLUSIONS
One of the mechanisms by which H. pylori infection inhibits gastric acid secretion is increased release of PGE2 produced by COX-2, which is induced by H. pylori infection.
Xiao
F
F
First Dept. of Medicine, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu, 431-3192, Japan.
Furuta
T
T
Takashima
M
M
Shirai
N
N
Hanai
H
H
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D017308:Etodolac / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000503:physiopathology; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010544:Peroxidases / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013047:Specific Pathogen-Free Organisms
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D017308:Etodolac; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone