A new gastric ulcer model in rats produced by ferrous iron and ascorbic acid injection

We developed a new gastric ulcer model in which the ulcers are induced by the local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the gastric wall. These ulcers resemble human gastric ulcers that penetrate the muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid alone, gastric ulcers did not form, whereas penetrating ulcers were produced by the simultaneous injection of the Fe/ASA solution in a dose-dependent manner. Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h after the injection of the Fe/ASA solution. This increase in lipid peroxides preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD, recombinant human CuZnSOD) significantly reduced the size of the ulcers and inhibited the accumulation in lipid peroxides in the gastric mucosa, while treatment with apo-SOD or heat-inactivated SOD did not. These results suggest that lipid peroxidation mediated by oxygen radicals plays a crucial role in the pathogenesis of the gastric ulceration induced by the Fe/ASA solution.