geranylgeranylacetone and Duodenal-Ulcer

Since gastric mucosal lesions are frequently encountered in patients with liver disease, we measured the levels of gastric mucosal hexosamine. In chronic hepatitis patients, hexosamine levels were reduced in both the antrum and corpus as compared with those in normal controls, while values in the advanced liver cirrhosis group (total bilirubin greater than 5 mg/dl) were lower than in the less advanced group. Although the presence or absence of esophageal varices had no influence on hexosamine, higher concentrations were found in patients with the red color sign (+) in comparison with those with negative red color sign (-). One month after endoscopic injection sclerotherapy of esophageal varices, hexosamine did not change, but decreases were seen in both the antrum and corpus at 3 months. We observed an increase in gastric mucosal blood flow after treatment with teprenone, a new antiulcerative agent, in normal controls. Gastric mucosal hexosamine increased significantly after teprenone treatment in both chronic hepatitis and liver cirrhosis groups. From these results, we conclude that hexosamine has a defensive action against gastric lesions in various liver diseases.

Topics: Anti-Ulcer Agents; Carcinoma, Hepatocellular; Diterpenes; Duodenal Ulcer; Female; Gastric Mucosa; Hexosamines; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Stomach Ulcer

Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water-immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone.

Topics: Animals; Anti-Ulcer Agents; Cimetidine; Diterpenes; Duodenal Ulcer; Female; Gastric Mucosa; Gastrointestinal Motility; Guinea Pigs; Immersion; Male; Oximes; Piperazines; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Psychological

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.

Topics: Animals; Disease Models, Animal; Diterpenes; Duodenal Ulcer; Female; Gastric Acid; Male; Rats; Stomach Ulcer; Terpenes; Wound Healing