Inhibition by aspirin of gastrointestinal toxicity induced by indomethacin in polyarthritic rats
Rosenbaum, E.S.; Barbieri, E.J.
Toxicology and Applied Pharmacology 49(3): 535-541
1979
ISSN/ISBN: 0041-008X PMID: 473219 Document Number: 140035
Methods were employed for examining the gastrointestinal toxicity of indomethacin, aspirin and combinations of these drugs in adjuvant-induced polyarthritic rats. Significant toxicity, primarily associated with the small intestine, was observed at oral doses between 4 and 8 mg/kg per day of indomethacin alone. Lethality was observed with doses of indomethacin from 5-8 mg/kg per day. Adverse gastrointestinal effects of aspirin, 32-500 mg/kg per day, orally, were minimal (erythema and bleeding of the stomach mucosa and, on occasion, an intestinal ulceration); deaths occurred at 625 mg/kg and above. Polyarthritic rats were treated with various combinations of aspirin and indomethacin had significantly less gastrointestinal damage than animals treated with identical doses of indometacin alone. Aspirin, 100 mg/kg and above, virtually abolished the dose-related indomethacin-induced gastrointestinal toxicity in the doses that were studied. At 32 mg/kg aspirin, the parallel shift in the indomethacin dose-toxicity curve suggested that the interaction between these 2 drugs is the result of competitive antagonism.