The effect of food intake and gut bacterial flora on gastrointestinal lesions caused by oral indometacin (IND) was studied in rats. A dose of 10 mg/kg IND caused no intestinal lesions when the animals were starved before and after treatment; it produced moderate lesions when the animals were continuously fed and maximal lesions when the animals were fed in the postdrug period after starvation in the predrug period. Under germ-free conditions, 15 mg/kg IND induced significantly less intestinal lesions than under specific pathogen-free conditions. The differences in the magnitude of intestinal lesions under the varying feeding and maintenance conditions were not associated with different IND concentrations in the jejunal mucosa. The dose of 10 mg/kg IND produced most gastric lesions when the animals were previously starved for 24 h and subsequently fed, medium lesions in continuously starved animals and only a few lesions in animals fed before and after IND. The disposition of IND from the gastric mucosa did not differ under the different feeding conditions. As the dose of IND is high enough to inhibit prostaglandin synthesis, it was concluded that additional factors are important for the development of gastrointestinal lesions caused by IND. Secondary bile acids in conjunction with IND are important for the development of intestinal lesions, while gastric acid influences the intensity of gastric lesions.
The effect of 16, 16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 μg/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.