Biol. Pharm. Bull. 29(4) 675—683 (2006)

tion 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 C48/80 treatment that the development of gastric mucosal lesions occurs with decreases in Se-glutathione peroxidase (Se-GSHpx) activity and vitamin E and hexosamine levels and increases in neutrophil infiltration, xanthine oxidase (XO) activity, and lipid peroxide level in the gastric mucosal tissue and that gastric mucosal blood flow changes like ischemia-reperfusion during gastric mucosal lesion development. We have also shown in rats treated once with C48/80 that neutrophils infiltrating into the gastric mucosal tissue participate in gastric mucosal lesion formation and progression, while the xanthine–XO system in the gastric mucosal tissue takes part mainly in the lesion progression. Furthermore, it has been shown in rats treated once with C48/80 that acutely released endogenous serotonin contributes to gastric mucosal lesion formation, while released endogenous histamine mainly contributes to the lesion progression, although gastric acid plays no important role in the pathogenesis of the C48/80-induced gastric mucosal lesion. Ascorbic acid (vitamin C) is a water-soluble antioxidant and it scavenges reactive oxygen species (ROS), such as superoxide radical (O2 ), hydroxyl radical (OH . ), hydrogen peroxide (H2O2), singlet oxygen, and hypochlorus acid, by itself and also supports the chainbreaking antioxidant action of vitamin E by reducing vitamin E radical to vitamin E at the liquid/aqueous interface. In addition, ascorbic acid prevents neutrophil adherence to endothelium by scavenging ROS derived from activated neutrophils. Our recent reports have shown that ascorbic acid content decreases with a concomitant decrease in vitamin E content during lesion progression in the gastric mucosa of rats treated once with C48/80 and that gastric mucosal ascorbic acid plays a critical role in the progression of C48/80-induced gastric mucosal lesions, which is closely associated with its antioxidant and anti-inflammatory actions in the gastric mucosa. Vitamin E is a lipid-soluble antioxidant and it functions as a chain-breaking antioxidant for lipid peroxidation in cell membranes and also as a scavenger of ROS such O2 , OH. , and singlet oxygen. Vitamin E exerts an anti-inflammatory action by inhibiting the production O2 in activated neutrophils, adhesion of neutrophils to endothelial cells, and transendothelial migration of neutrophils. Yoshikawa et al. reported that both a decrease in gastric mucosal vitamin E level and an increase in gastric mucosal lipid peroxidation occurred during the development of ischemia-reperfusion-induced gastric mucosal injury in rats and that the severity of ischemia-reperfusion-induced gastric mucosal injury was enhanced in vitamin E-deficient rats. Naito et al. have shown in nitric oxide-depleted rats that vitamin E plays an important role in protecting against ischemia-reperfusion-induced gastric mucosal injury, and have suggested that this gastroprotective effect of vitamin E is due to not only its antioxidant action but also its inhibitory action on neutrophil infiltration into the gastric mucosa. Al-Dhohyan and Al-Tuwaijri reported that a single oral pre-adminApril 2006 675 Biol. Pharm. Bull. 29(4) 675—683 (2006)