Effects of prostaglandins on hydrocortisone-induced delayed healing of chronic gastric ulcers in the rat

Abstract

We have previously shown that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of 16,16-dimethylprostaglandin E2 or TRY-200, a stable prostaglandin I2 analogue, on the delayed healing by hydrocortisone (HC) of chronic gastric ulcers in rats. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by serosal application of 100% acetic acid. The rats were randomly divided into six groups: (1) saline, (2) saline, HC-treated, (3) 10 micrograms/kg of 16,16-dimethylprostaglandin E2, (4) TRY-200, a stable prostaglandin I2 analogue, at 5 micrograms/kg, or (5) 10 micrograms/kg, or (6) 30 micrograms/kg. All rats, except for control, were given daily intraperitoneal injection of 2.5 mg/kg of HC sodium phosphate. Tested drugs were administered intragastrically twice a day for 2 weeks. Rats were killed 14 days later and ulcer size was measured. Chronic administration of HC sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with TRY-200 at 10 or 30 micrograms/kg abolished the deleterious effect of steroids, whereas 16,16-dimethylprostaglandin E2 had no effect. These results indicate that prostaglandin I2 is more effective than prostaglandin E2 in reversing the delayed healing by steroids of chronic gastric ulcers in the rat.