Effect of vitamin E supplementation on prostaglandin concentrations in aspirin-induced acute gastric injury in aged rats.
Nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin, frequently cause gastric mucosal injury in the elderly. Impairment of prostaglandin synthesis is a crucial step by which aspirin attenuates mucosal defense capacity. Vitamin E has been shown to decrease prostanoid concentrations, which implies an ulceropermissive effect of vitamin E. To assess the effect of vitamin E on aspirin-induced gastric injury and mucosal prostanoid concentrations, 20 male rats aged 20 mo were divided into two groups and fed diets containing either 30 (physiologic requirement) or 500 mg all-rac-alpha-tocopheryl acetate/kg. After 6 wk, all rats received two intragastric doses of aspirin (1.4 mumol/kg body wt). A third group of six animals fed the high-vitamin E diet received a vehicle solution without aspirin. Mucosal samples for vitamin E and prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane A2 measurements were collected. The prevalence and degree of mucosal lesions were not significantly different among all groups. Rats fed the high-vitamin E diet had significantly higher mucosal vitamin E concentrations than rats fed the low-vitamin E diet. Mucosal concentrations of all three prostanoids were 95% lower in aspirin-treated rats than in controls (P = 0.0001 in all instances). The high-vitamin E diet group had significantly lower mucosal 6-keto-prostaglandin F1 alpha concentrations (P = 0.02) than the low-vitamin E diet group, indicating decreased prostacyclin formation, whereas concentrations of prostaglandin E2 and thromboxane A2 were similar in the aspirin-treated groups. Aspirin markedly reduced mucosal prostanoid concentrations in rats, without apparent effects on gastric injury, whereas vitamin E supplementation significantly reduced mucosal 6-keto-prostaglandin F(1 alpha) concentrations. Nevertheless, vitamin E supplementation did not result in more gastric injury in aspirin-treated rats than in controls.
Stickel
F
F
Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston MA 02111, USA.
Meydani
M
M
Wu
D
D
Bronson
R
R
Martin
A
A
Smith
D
D
Meydani
S N
SN
Russell
R M
RM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000284:Administration, Oral; D000375:Aging / Q000097:blood / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011453:Prostaglandins / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000097:blood / Q000378:metabolism; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*
D011453:Prostaglandins; D014810:Vitamin E; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001241:Aspirin