PREVENTION OF GASTRIC-ULCER RELAPSE INDUCED BY INDOMETHACIN IN RATS BY A MUTEIN OF BASIC FIBROBLAST GROWTH-FACTOR

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H -2-receptor antagonists (H-2-RAs) on ulcer relapse in this model. In m ale SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starti ng 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm(2), respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administrati on period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/k g) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The ag gravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. Wh en the drugs were co-administered with indomethacin for 2 weeks, the a ggravation was significantly prevented by ranitidine and mildly inhibi ted by cimetidine and TGP-580. Both TGP-580 and H-2-RAs can prevent th e ulcer relapse induced by indomethacin but via different modes of act ion: TGP-580 inhibits relapse mainly by acting on the process of heali ng, while H-2-RAs act mainly on the process of aggravation.