Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1986-4-30
pubmed:abstractText
Rats were given a single intragastric administration of the prodrug sulindac (4.0 mg/kg) or its sulfide (1.0, 2.0, 4.0, or 8.0 mg/kg) or sulfone (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 rats received an equal volume of propylene glycol vehicle or nothing po. Other rats received 200 mg/kg acetylsalicylic acid (ASA) with or without stress, to compare the gastrointestinal effects of sulindac metabolites with those of a known non-steroidal anti-inflammatory agent. The sulfide metabolite exacerbated stress-induced gastric glandular ulcer incidence and severity in a dose-related manner relative to all groups except the ASA-stress group, which exhibited the greatest amount of gastric damage. The sulfone metabolite did not potentiate ulcer 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 rats exhibited a similar degree of stress-induced gastric damage. It appears that the prodrug does not significantly enhance stress-related gut disease, but that the active sulfide metabolite does. Although the clinical literature suggests that the sulfone metabolite is inactive, the present results suggest otherwise. While this metabolite did not, by itself, induce gastric damage at higher doses, sulfone did exacerbate stress ulcer formation. This is the only report of which we are aware, indicating a possible toxic effect of the sulfone metabolite.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
386-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
The effects of sulindac and its metabolites on acute stress-induced gastric ulcers in rats.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't