Omeprazole prevents indomethacin-induced gastric ulcers in rabbits.
BACKGROUND
The role of gastric acid in the development of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers is unclear. The aim of this study was to determine the effect of the proton pump inhibitor omeprazole on the formation of indomethacin-induced gastric ulcers in a rabbit model.


METHODS
Twenty-four rabbits were randomly divided into four groups and treated as follows: vehicle for indomethacin; vehicle for omeprazole; indomethacin (20 mg/kg b.d. subcutaneously for seven doses); and indomethacin plus omeprazole (both at 20 mg/kg b.d. subcutaneously for seven doses). On day 4 (after the seventh injection), rabbits were sacrificed, and gastric mucosal injury and prostaglandin formation were assessed.


RESULTS
Subcutaneous administration of 20 mg/kg omeprazole b.d. caused a profound suppression of gastric acidity (i.e. pH above 5.0 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by indomethacin despite significant (> 80%) inhibition of gastric mucosal prostaglandin E2 (PGE2) formation.


CONCLUSIONS
We conclude from these observations that gastric acid plays a critical role in the formation of indomethacin-induced gastric ulcers in rabbits.
Lee
M
M
University of Texas Health Science Center at San Antonio, Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Kallal
S M
SM
Feldman
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D015232:Dinoprostone / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity*; D009853:Omeprazole / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors; D011706:Pyloric Antrum / Q000187:drug effects; D011817:Rabbits; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D015232:Dinoprostone; D009853:Omeprazole; D007213:Indomethacin