The significance of removing oxygen-derived free radicals in the treatment of acute and chronic duodenal ulceration in the rat

Abstract

Abstract Rats infused for 24 h with pentagastrin (4 μg kg−1 min−1) and carbachol (0.8 μg kg−1 min−1) developed acute duodenal ulceration (100%) and hyperchlorhydria (69 ± 5.3 μmol h−1 vs 14 ± 0.9 μmol h−1, P < 0.001, n = 10). The animals were then given daily by gavage, saline, allopurinol with dimethyl sulphoxide (DMSO) or cysteine with methyl methionine sulphonium bromide (MMSB). Two days after the infusion, 10 rats (100%) given saline and 7 rats (70%) given allopurinol and DMSO, or cysteine and MMSB, showed duodenal ulceration. Five days after the infusion, 8 rats (80%) given saline, 3 rats (30%) given allopurinol and DMSO, and 2 rats (20%) given cysteine and MMSB had duodenal ulceration. Seven days after the infusion, only 5 rats (50%) given saline still had duodenal ulceration. Daily intramuscular injection of reserpine (0.1 mg kg−1) for 6 weeks produced chronic duodenal ulceration (90%) and hyperchlorhydria (47 ± 31 μmol h−1 vs 12 ± 0.9 μmol h−1, P < 0.001, n = 10). Animals were then given daily by gavage, saline, allopurinol and DMSO, or cysteine and MMSB. Five days after reserpine, 10 rats (100%) given saline, 8 rats (80%) given allopurinol and DMSO, and 7 rats (70%) given cysteine and MMSB showed duodenal ulceration. Ten days after reserpine, 9 rats (90%) given saline, 3 rats (30%) given allopurinol and DMSO, and 4 rats (40%) given cysteine and MMSB had duodenal ulceration. Fifteen days after reserpine, 8 rats (80%) receiving saline and only one rat (10%) receiving allopurinol and DMSO or cysteine and MMSB had duodenal ulceration. Twenty days after the reserpine treatment only 6 rats (60%) given saline still had duodenal ulceration. The results show that removing oxygen-derived free radicals stimulates the healing of acute and chronic duodenal ulceration in the rat.