Role of Sulfhydryl-Containing Agents in the Healing of Erosive Gastritis and Chronic Gastric Ulceration in the Rat

Abstract

One milliliter of 1, 2, or 5% DL-cysteine (cysteine) or DL-methionine methylsulfonium chloride (MMSC) was instilled into the rat stomach 1, 24, and 48 h after giving ethanol (1 mL of 40% solution) by gavage. One hour following the administration of ethanol, gastric mucosal injury was seen in all the animals (22.6 ± 1.1 mm2, mean ± SEM; n = 10). Twenty-four hours after giving the ethanol, all the rats treated with cysteine or MMSC still had the mucosal injury. Treatment with 2% cysteine or MMSC significantly (p < 0.01) reduced the extent of this injury (10.2 ± 0.6 and 10.1 ± 0.5 mm2, respectively, versus 20.7 ± 1.2 mm2, mean ± SEM; n = 10), an action that was similarly achieved by the 5% solutions (10.1 ±0.5 and 9.9 ± 0.3 mm2, respectively, versus 20.7 ± 1.2 mm2, mean ± SEM; n = 10). Forty-eight hours following the administration of ethanol, 30% of the animals given 1% cysteine or MMSC still had gastric mucosal injury, which was significantly (p < 0.001) less extensive than that seen with ethanol alone (3.8 ± 0.3 and 4.1 ± 0.3 mm2, respectively, versus 13.1 ± 0.8 mm2, mean ± SEM; n = 10). At this time period, however, none of the animals treated with 2 or 5% solutions of cysteine or MMSC still had any injury. Healing of the ethanol-induced injury was confirmed microscopically and was achieved by regeneration. Chronic gastric ulceration was produced in the rat by administering 5 mg/kg of reserpine ip every day for 5 days, then housing the animals for 2 weeks. Cysteine and MMSC (1 mL by gavage daily) demonstrated a dose-dependent and time-related power to stimulate the healing of this ulceration. After gavaging for 5 days, 80% of the rats given 1% cysteine and 70% of those given 1% MMSC had gastric ulceration, whereas only 20% of the animals given 10% solutions had the ulceration. After gavaging for 10 days, 20% of the rats given 1% cysteine and 30% of those given 1% MMSC had gastric ulceration, whereas none gavaged with 5 or 10% solutions of these agents still had any ulceration. At this stage, 70% of the animals gavaged with distilled water still had the ulceration. These cysteine and MMSC actions were independent of any effect on the gastric acid secretion. The results show that sulfhydryl-containing agents stimulate the healing of ethanol-induced acute gastric mucosal injury and chronic gastric ulceration in the rat.