Mitsunori Yasuda

Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats.

The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric erosions and concentration of lipid peroxides in the gastric mucosa increased with time after administration of indomethacin (20 mg/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significantly decreased and the activity of glutathione peroxidase, an important enzyme to scavenger of lipid peroxides, was inhibited by the administration of indomethacin. Treatments with superoxide dismutase and catalase inhibited the increases in gastric mucosal erosions and lipid peroxides in the gastric mucosa, and the reduction of serum alpha-tocopherol. Treatment with these scavengers did not improve the decreased glutathione peroxidase activity. These findings suggest that active oxygen species and lipid peroxidation play an important part in the pathogenesis of gastric mucosal injury induced by indomethacin, and that the decreased glutathione peroxidase activity aggravated the injury due to accelerated accumulation of hydrogen peroxide and lipid peroxides in the gastric mucosal cell.

Effect of Zinc-Carnosine Chelate Compound (Z-103), A Novel Antioxidant, on Acute Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

The protective effect of a novel synthetic zinc-carnosine chelate compound, zinc N-(3-aminopropionyl)-L-histidine (Z-103), on the gastric mucosal injury induced by ischemia-reperfusion was studied in rats. Ischemia and reperfusion injury was produced on the rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 30 min. The decrease in the gastric mucosal blood flow was not influenced by the treatment with Z-103. The increase in total area of the erosions on the stomach after ischemia-reperfusion and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by the oral administration of Z-103. In addition, Z-103 inhibited lipid peroxidation of rat brain homogenate and liver microsome in vitro. These results suggest that the protective effect of Z-103 against the aggravation of gastric mucosal injury induced by ischemia-reperfusion may be due to its inhibitory effect on lipid peroxidation.

Role of Free Radicals and Lipid Peroxidation in Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

Ischemia and reperfusion is of the greatest importance in the pathology of various diseases. This study was designed to investigate the role of oxygen-derived free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. Gastric mucosal injury, such as spotty and linear hemorrhagic erosions, was seen in rats 60 min of the reperfusion following 30 min of ischemia. Thiobarbituric acid (TBA) reactants in the gastric mucosa were increased after the reperfusion. The increase in gastric mucosal lesions and TBA reactants were significantly inhibited by the treatment with SOD+ catalase and allopurinol. These results suggest that oxygen-derived free radicals and lipid peroxidation may play an important role in the pathogenesis of acute gastric mucosal lesions induced by ischemia-reperfusion.