The influence of paracetamol on the erosive activity of indomethacin in the rat stomach.
Indomethacin induced erosions in the glandular part of the rat stomach in a dose-dependent manner. Gastric erosions became apparent about 15 min after administration of indomethacin and the damage was maximal at about 4 h. The erosive activity of indomethacin administered subcutaneously was similar to that after oral administration, confirming the data of other authors. The erosive activity of subcutaneously applied aspirin, however, was far less than that of oral administered aspirin and it was not dose dependent. In a dose-dependent manner, paracetamol reduced the incidence of gastric erosions induced with indomethacin; this effect was independent of the route of administration of either drug. Paracetamol was also effective when given 0.5 or 1 h before indomethacin. Orally administered paracetamol also reduced the incidence of gastric erosions induced with aspirin but after subcutaneous administration, paracetamol had no protective effect. The differences between the erosive activities of indomethacin and aspirin are discussed with emphasis on the differentiating influence of paracetamol on the incidence of gastric erosions. Direct contact with the mucosa is apparently more important for the erosive activity of aspirin than for that of indomethacin. Possible mechanisms by which paracetamol exerts its protective activity are proposed.
D000082:Acetaminophen / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013997:Time Factors
D000082:Acetaminophen; D001241:Aspirin; D007213:Indomethacin