CORTICOSTEROIDS REDUCE REGENERATIVE REPAIR OF EPITHELIUM IN EXPERIMENTAL GASTRIC-ULCERS

The association between corticosteroid treatment and gastric ulcer hea ling is controversial. The effects of corticosteroids on experimental ulcer healing in the rat were studied and the effect of coadministrati on of a prostaglandin E(1) analogue was determined. Forty male adult r ats were divided into five groups and pretreated for 10 days as follow s: (a) control, (b) prednisolone (10 mg/kg), (c) prednisolone and miso prostol (300 mu g/kg), (d) misoprostol, and (e) indomethacin (2 mg/kg) Gastric ulcer was induced by applying a cryoprobe to the serosal surf ace of the stomach. Healing was assessed by determining the ulcer size at three and six days. Mucosal regenerative activity at the ulcer edg e was assessed by quantitating DNA synthesis in cells by immunohistoch emical techniques using monoclonal antibodies to detect expression of proliferating cell nuclear antigen (PCNA) and incorporated 5-bromo-5-i ododeoxyuridine (BrdU). Compared with control rats, the rate of healin g and the mucosal regenerative activity were significantly reduced in rats treated with prednisolone and indomethacin (p < 0.05). Coadminist ration of misoprostol and corticosteroids reversed the delay in healin g and the reduction in mucosal regeneration induced by corticosteroids alone. With misoprostol alone, the ulcer size and the number of epith elial cells that actively synthesised DNA did not differ from control animals. A comparison between the two immunohistochemical markers of c ell proliferation showed a highly significant correlation between the two techniques p < 0.005), indicating that the PCNA technique should p rove valuable in assessing regeneration in experimental ulcer disease.