The effects of sulindac and its metabolites on acute stress-induced gastric ulcers in XXXX .

@entity5879 @entity2771 @entity1281 @entity1819 @entity117 @entity1066 @entity35 @entity3287
@entity35 were given a single intragastric administration of the prodrug sulindac (4.0 mg/kg) or its @entity3287 (1.0, 2.0, 4.0, or 8.0 mg/kg) or @entity5879 (1.0, 2.0, 4.0, or 8.0 mg/kg) metabolites and were then subjected to acute stress in the form of immobilization for 3 hr in a cold environment. Control @entity35 received an equal volume of @entity2771 vehicle or nothing po. Other @entity35 received 200 mg/kg @entity117 ( @entity1281 ) with or without stress, to compare the gastrointestinal effects of sulindac metabolites with those of a known non-steroidal anti-inflammatory agent. The @entity3287 metabolite exacerbated stress-induced gastric glandular @entity1066 incidence and severity in a dose-related manner relative to all groups except the ASA-stress group, which exhibited the greatest amount of @entity1819 . The @entity5879 metabolite did not potentiate @entity1066 incidence or severity beyond control (stress only) levels at lower doses. However, at 4.0 and 8.0 mg/kg, the observed ulceration was greater than that seen in stressed but otherwise untreated animals. Sulindac, vehicle, and otherwise untreated @entity35 exhibited a similar degree of stress-induced @entity1819 . It appears that the prodrug does not significantly enhance stress-related gut disease, but that the active @entity3287 metabolite does. Although the clinical literature suggests that the @entity5879 metabolite is inactive, the present results suggest otherwise. While this metabolite did not, by itself, induce @entity1819 at higher doses, @entity5879 did exacerbate stress @entity1066 formation. This is the only report of which we are aware, indicating a possible toxic effect of the @entity5879 metabolite.
