Mepirozole, a basic antiinflammatory
drug and duodenal ulcerogen in laboratory animals, macroscopically protected the gastric mucosa of rats from HCl-
ethanol-induced damage in a dose-dependent manner. These effects were evident when the agent was given orally, intraperitoneally, or subcutaneously at 3 or 10 mg/kg 0.5 hr before HCl-
ethanol administration. Histologically, the surface epithelial and pit cells were not protected by
mepirizole, but most of the mucosal cells located in the deeper portions were well preserved. Gastric acid secretion in the pylorus-ligated or acute
fistula preparation was not affected by 10 mg/kg of
mepirizole. Gastric motility determined by a balloon method was dose-dependently inhibited by the agent.
Mepirizole protection was significantly reduced by pretreatment with subcutaneous
indomethacin (5 mg/kg) and
N-ethylmaleimide (10 mg/kg). The gastric motility inhibited by
mepirizole was not reversed by
indomethacin and
N-ethylmaleimide treatment. These results suggest that the mechanism underlying
mepirizole protection relates to both endogenous
prostaglandins and
sulfhydryl compounds present in the gastric mucosa, but does not relate to an inhibition of gastric motility.
Dulcerozine and other basic antiinflammatory drugs (
tiaramide,
tinoridine, and
benzydamine) given either orally or intraperitoneally
at 10-100 mg/kg also dose-dependently prevented the development of HCl-
ethanol-induced lesions.
Mepirizole and other basic antiinflammatory drugs are cytoprotective in the rat stomach.