Biol. Pharm. Bull. 28(8) 1424—1430 (2005)

clinically used for the treatment of gastric ulcers and gastritis. Takagi and Yano reported that when gefarnate was orally administered to fasted rats for 5 d, the level of hexosamine, an index of gastric mucus, in the pyloric tissue of the stomach increased and that the reduction of hexosamine content in the gastric pyloric tissue of rats with 3 d of water immersion restraint stress (WIRS) was prevented by daily simultaneous administration of gefarnate. There are several reports showing that gefarnate exerts a protective effect against acute gastric mucosal lesions in various in vivo experimental models such as gastric mucosal lesions induced by histamine–antihistamine, immobilization, reserpine, fasting, ethanol, asprin, HCl–asprin, HCl–ethanol, HCl–taurocholate, and WIRS. Hara et al. showed that when pylorus-ligated rats with oral HCl–asprin treatment received a single oral pre-administration of gefarnate, this drug exerted a protective effect against gastric mucosal lesions with attenuation of decreased gastric mucosal hexosamine content. In addition, Kobayashi et al. reported that gefarnate prevented WIRS-induced ulcer formation by inhibiting the reduction of endogenous prostaglandin E2 and prostacyclin (prostaglandin I2) levels. Teprenone (geranylgeranylacetone), of which chemical structure is similar to that of gefarnate, is an anti-ulcer drug developed in Japan. This drug is clinically used for the treatment of gastric ulcers and gastritis. Teprenone is known to stimulate gastric mucus synthesis and secretion in rat gastric cultured cells and in the gastric tissue of rats. There are several reports showing that teprenone exerts a protective effect against acute gastric mucosal lesions in various in vivo experimental models, such as gastric mucosal lesions induced by asprin, cold restraint stress, WIRS, and HCl–taurocholate, through preservation of gastric mucus synthesis and secretion. It has been shown that teprenone protects cultured rat gastric mucosal cells against reactive oxygen species (ROS) such as superoxide radical (O2 ) by increasing the production of mucus. In addition, it has been shown in vitro that teprenone inhibits the adhesion of neutrophils to endothelial cells and the expression of CD11b/CD18a, an adhesion molecule, on neutrophils when the neutrophils are activated by Helicobacter pylori water extract. We reported that teprenone exerted protective and preventive effects against acute gastric mucosal lesions in rats with WIRS not only by preservation of gastric mucus synthesis and secretion but also by inhibition of neutrophil infiltration and enhanced lipid peroxidation in the gastric mucosa. Compound 48/80 (C48/80) is known to cause degranulation of connective tissue mast cells, but not mucosal mast cells, with release of serotonin and histamine from the cells. We have shown in rats with a single treatment of C48/80 that the development of gastric mucosal lesions occurs with decreases in Se-glutathione peroxidase activity and vitamin E and hexosamine contents and increases in neutrophil infiltration, xanthine oxidase (XO) activity, and lipid peroxide content in the gastric mucosal tissue and that gastric mucosal blood flow is reduced with gastric mucosal lesion formation, while the decreased blood flow is recovered with the lesion progression. We have also shown in rats treated