Protective effect of acetaminophen against aspirin- and ethanol-induced damage to the human gastric mucosa.
Aspirin and ethanol damage the gastric mucosa in humans, whereas acetaminophen does not. Acetaminophen increases prostacyclin activity in animals and thus may increase endogenous prostaglandin synthesis. The effect of acetaminophen was examined in five healthy subjects after intragastric aspirin or ethanol. Hydrogen and sodium ion fluxes were measured in the pylorus-occluded stomach that prevents duodenogastric reflux and gastric fluid losses. Studies were in random order and on 8 separate days. Potential difference was measured throughout and mucosal erosions were endoscopically quantitated (endoscopist masked, no premedication). The isoosmolar test solution (200 ml, 100 mM HC1, 54 mM mannitol, [14C]polyethylene glycol) was instilled into the stomach and removed 15 min later for four 15-min periods. Either aspirin (1300 mg) or ethanol (20% vol/vol) was added to the test solution only during the second 15 min. Acetaminophen (2600 mg) was given orally 1 h before aspirin or ethanol administration. To determine if the effect of acetaminophen was related to prostaglandin synthesis, prostaglandin production was inhibited with indomethacin (50 mg orally 12 h and 1 h before acetaminophen). Aspirin and ethanol alone each produced significant changes in net hydrogen and sodium fluxes, potential difference, and endoscopic changes. Acetaminophen significantly inhibited hydrogen ion flux, change in potential difference, and endoscopic damage; however, it did not totally abolish these changes. The protective effect of acetaminophen was abolished by pretreatment with indomethacin, suggesting that the effect of acetaminophen is likely to be prostaglandin-mediated. Indomethacin alone was without effect. These results demonstrate that oral acetaminophen protects the human gastric mucosa against the damaging effects of aspirin and ethanol.
D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D001241:Aspirin / Q000037:antagonists & inhibitors*; D004341:Drug Evaluation; D000431:Ethanol / Q000037:antagonists & inhibitors*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007474:Ion Exchange; D008297:Male; D011199:Potentiometry; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D011448:Prostaglandin Antagonists; D000082:Acetaminophen; D000431:Ethanol; D012964:Sodium; D001241:Aspirin; D007213:Indomethacin