Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats.
OBJECTIVE
Aspirin and other nonsteroidal anti-inflammatory drugs are known to cause gastrointestinal mucosal injury in humans and animals. The present study was designed to determine the effect of aging on gastric mucosal eicosanoid formation and aspirin-induced injury in Fischer 344 rats.


METHODS
In part 1 of the study, rats of three different age groups (3, 12, and 21 months) were killed after an overnight fast, and gastric mucosal formation of prostaglandins and leukotrienes was determined. In part 2, rats of various ages were killed 3 hours after receiving aspirin (100 mg/kg intragastrically) or vehicle (for controls). Gastric mucosal eicosanoid formation and gross mucosal injury were assessed.


RESULTS
Gastric mucosal prostaglandin formation decreased with aging, whereas no significant changes in mucosal leukotriene formation were noted in any age groups. No gastric mucosal lesions were present in any rats treated with vehicle alone. In contrast, aspirin caused significant mucosal injury in all age groups, but significantly more mucosal lesions were noted in the older rats.


CONCLUSIONS
These observations indicate that gastric mucosal prostaglandin synthesis decreases with aging in rats and that aged animals are more susceptible to aspirin-induced acute gastric mucosal injury.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
M
M
Lee
M
M
Feldman
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000009:adverse effects*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D015289:Leukotrienes; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D001241:Aspirin