Prevention of Gastric Ulcer Relapse Induced by Indomethacin in Rats by a Mutein of Basic Fibroblast Growth Factor

[摘要] References(38)Cited-By(3)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 H2-receptor antagonists (H2-RAs)on ulcer relapse in this model. In male 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 starting 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 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg)and TGP-580 (0.1 mg/kg)for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

[学科分类] 药理学

[关键词] Gastric ulcer relapse;Basic fibroblast growth factor (bFGF);bFGF mutein CS23;TGP-580;Histamine H2-receptor antagonist