Prevention and healing of experimental indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine.
BACKGROUND
Ebrotidine is a new H2 receptor antagonist that potentiates the gastric mucosal barrier.


OBJECTIVE
To compare ebrotidine with other anti-secretory drugs in the prevention and healing of indomethacin-induced gastric lesions.


METHODS
Three different models of indomethacin-induced gastric lesions were used. (1) Fasted rat model: indomethacin was intra-gastrically administered in rats pre-treated with different doses of the anti-secretory drugs. (2) Re-fed rat model: rats orally treated with different doses of anti-secretory drugs had free access to chow pellets and were then treated with parenteral indomethacin. (3) Healing model: either oral or parenteral anti-secretory drugs were given after indomethacin administration. Computer-assisted analysis of the area of damage was expressed as ulcer index. Gastric secretion was evaluated in the pylorus-ligated rat model.


RESULTS
Inhibition of acid secretion was in the order omeprazole > ebrotidine = ranitidine. Ebrotidine at the highest dose used (100 mg/kg) and omeprazole, but not ranitidine, significantly prevented indomethacin-induced corpus (fasted rat) and antrum (re-fed rat) gastric lesions. In the ulcer healing model, oral administration of omeprazole and both ranitidine and ebrotidine at the highest dose used improved the ulcer index. The parenteral administration of these drugs had a lesser effect than the oral route and was in the order ebrotidine > omeprazole > ranitidine.


CONCLUSIONS
Ebrotidine is effective in both the prevention and healing of indomethacin-induced experimental gastric lesions. In these models, the effect of ebrotidine is comparable to omeprazole and more effective than ranitidine.
Arroyo
M T
MT
Services of Gastroenterology and Research Unit (UMI), Hospital Clínico Universitario, University of Zaragoza, Spain.
Lanas
A
A
Sáinz
R
R
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005750:Gastric Juice / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D007213:Indomethacin; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013844:Thiazoles; D011899:Ranitidine; D009853:Omeprazole; C075156:ebrotidine; D007213:Indomethacin