Role of gastric mucosal eicosanoid production in the cytoprotection induced by nitecapone.
Nitecapone (3-100 mg/kg orally) dose-dependently (40-97%) decreased the macroscopic gastric lesions induced by ethanol, NaOH, or HCl in the rat. The duration of protection was long, being still 70% at 6 h after dosing. Nitecapone (10-100 mg/kg orally) induced at 1 h after dosing a significant and dose-dependent increase in gastric mucosal prostaglandin E2 release. After the dose of 30 mg/kg the release was sixfold at 2 h and threefold at 12 h. Colloidal bismuth subcitrate (30 mg/kg) stimulated the prostaglandin E2 release only transiently, and sucralfate (400 mg/kg) showed only a tendency to stimulate the release. Indomethacin prevented the nitecapone-induced stimulation of prostaglandin E2 but was unable to counteract the cytoprotective activity of the compound. Nitecapone (30 mg/kg) also caused transient increase (twofold) in the release of 6-keto-prostaglandin F1 alpha and thromboxane B2 and a decrease in both basal and ethanol-induced release of leukotriene C4.
Aho
P A
PA
Orion-Farmos Pharmaceuticals, Orion Research Center, Espoo, Finland.
Lindén
I B
IB
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010422:Pentanones / Q000494:pharmacology*; D051381:Rats
D001095:Arachidonic Acids; D002396:Catechols; D010422:Pentanones; C057364:nitecapone; D015232:Dinoprostone