M Lee1, S M Kallal, M Feldman. 1. University of Texas Health Science Center at San Antonio, Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Abstract
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. CONCLUSION: We conclude from these observations that gastric acid plays a critical role in the formation of 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. CONCLUSION: We conclude from these observations that gastric acid plays a critical role in the formation of indomethacin-induced gastric ulcers in rabbits.
Authors: M Fornai; G Natale; R Colucci; M Tuccori; G Carazzina; L Antonioli; S Baldi; V Lubrano; A Abramo; C Blandizzi; M Del Tacca Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2005-08-04 Impact factor: 3.000
Authors: Aroha B Sánchez; Beatriz Clares; María J Rodríguez-Lagunas; María J Fábrega; Ana C Calpena Journal: Cells Date: 2020-01-10 Impact factor: 6.600