Prevention of antiinflammatory drug-induced gastric lesions in rats by Abbott-29590.

Abstract

Abbott-29590, an antiinflammatory compound with antipyretic and analgesic activity in test animals, did not produce any gastric lesions in the rat after oral doses up to 256 mg/kg. In contrast, gastric lesions were produced by oral doses of aspirin, indomethacin, and phenylbutazone; the ED95 values were 88, 13, and 260 mg/kg, respectively. Pretreatment with Abbott-29590 blocked the gastric damage produced by aspirin and indomethacin but not the ulceration produced by phenylbutazone. The ED50 values of Abbott-29590 for preventing the gastric lesions produced by aspirin, Abbott-29590, and exogenous 0.1 N HCl suggest that Abbott-29590 was additive with aspirin in its antiinflammatory activity while simultaneously blocking the gastric lesions produced by aspirin. The antiinflammatory activity of indomethacin in the carrageenin rat paw edema test was not altered by 30 minutes pretreatment with Abbott-29590, while phenylbutazone and Abbott-29590 were additive in antiinflammattory activity. Studies of gastric lesions produced by a combination of aspirin, Abbott-29590, and exogenous 0.1N HCl suggest that Abbott-29590 may tighten the gastric mucosal barrier.