Antiulcer effect of geranylgeranylacetone, a new acyclic polyisoprenoid on experimentally induced gastric and duodenal ulcers in rats.

Antinuclear effects of geranylgeranylacetone (GGA), new acyclic polyisoprenoid, on several types of experimental gastric and duodenal ulcers were studied in rats. The prophylactic administration of GGA (50--200 mg/kg p.o. or 12.5--50 mg/kg i.p.) reduced the gastric ulcers induced by the exposure to cold-restraint stress and by the administration of indomethacin, acetylsalicylic acid (ASA), prednisolone or reserpine and the duodenal ulcer after the administration of cysteamine, although it was not effective against Shay's ulcer. The curative treatment with GGA accelerated the healing process of the gastric ulcers induced by the topical application of acetic acid or thermocautery and by the administration of ASA with the exposure to cold-restraint stress. The antinuclear effect of GGA was more distinct than that of gefarnate in all types of experimental models studied. Carbenoxolone effectively reduced the gastric ulcer formation by cold-restraint stress when it was administered i.p. but not p.o., whereas GGA was effective either i.p. or p.o. GGA and gefarnate did not affect the gastric secretion in pylorus-ligated rats, whereas carbenoxolone definitely reduced the secretion of gastric juice and acid. Hexosamine content in the stomach was reduced by the exposure to cold-restraint stress. The pretreatment with GGA prevented the reduction in hexosamine contents in the superepithelial mucous layer and mucosal layer. These results may suggest a high possibility that GGA is useful for clinical treatment of peptic ulcers, probably through a mechanism of increasing defence force of the gastric mucosa.