Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats

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Abstract
The gastrointestinal toxicity of a single oral administration of five nonsteroidal anti-inflammatory agents (NSAIDs) to rats was compared, by a method using51Cr-labeled red blood cells (RBC), and by macroscopic and microscopic examination. From the profile of gastrointestinal bleeding, the NSAIDs could be divided into a group consisting of aspirin (ASA), oxaprozin (OXP) and 2-[4-(3-methyl-2-butenyl)phenyl]propionic acid (TA), which caused only a transient increase in fecal blood loss based on a gastric lesion, and another group including indomethacin (IM) and ibuprofen (IP), which produced a biphasic increase in the blood loss. The initial phase was caused not only by a gastric lesion but also an intestinal lesion, and the secondary phase originated only in the intestinal lesion. The order of potency causing blood loss was IM≫IP>ASA≫TA>OXP. The safety ratio of OXP and TA was shown to be more favorable than that of the other three drugs.