Effect of vitamin E (E) on prostaglandin (PG) levels in aspirin-induced acute gastric injury in old rats

Non-steroidal anti-inflammatory drugs such as aspirin (ASA) frequently cause gastric mucosal injury in the elderly. Impairment of PG synthesis is a crucial step by which ASA attenuates mucosal defense capacity. E has been shown to decrease PG and thromboxane (TXA₂) levels implying an ulceropermissive effect of E for which there is currently no evidence in the literature. Twenty old (20 mo) male Sprague-Dawley rats were divided into 2 groups of 10 and fed diets containing either 30 or 500 ppm E. After 6 wks, rats received 2 intragastric doses of ASA (250 mg/kg body weight) at a .1 hr interval. Six control rats fed the high E diet received vehicle only. All animals were sacrificed after 6 hrs, and mucosal injury was immediately assessed. Mucosal concentrations of 6-keto-PGFla, TXB2, respective stable metabolites of prostacyclin (PGI₂), TXA₂, and PGE₂ were measured by RIA. Prevalence and degree of mucosal lesions revealed no significant differences between the 3 groups. Rats fed the high E diet had higher mucosal E levels (p<0.001) as determined by HPLC. Rats that received ASA showed a 95% decrease in levels of all 3 prostanoids (p<0.0001). Comparing both ASA-treated groups, those fed the high E diet had significantly lower mucosal PGI₂ levels (4.5 ±0.8 vs. 6.2 ±1.8 ng/mL, p<0.02), whereas E had no effect on PGE2 or TXB2 levels. We conclude that 2 acute intragastric ASA doses markedly reduces mucosal prostanoids concentrations without apparent effect on gastric injury. While H supplementation significantly reduces mucosal PGI₂ levels, it does not result in further gastric injury in AS A-dosed animals.