title: Prevention of gastric ulcer relapse induced by indomethacin in rats by a mutein of basic fibroblast growth factor.
abstract: 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.
authors.affiliation: Pharmaceutical Research Laboratories, Takeda Chemical Ind., Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: R
authors.initials: R
authors.lastname: Maeda
authors.forename: I
authors.initials: I
authors.lastname: Murakami
authors.forename: I
authors.initials: I
authors.lastname: Inada
authors.forename: F
authors.initials: F
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Shino
mesh_terms: D019342:Acetic Acid / Q000008:administration & dosage / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D013270:Stomach / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D011994:Recombinant Proteins; C065198:protein CS23; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D002927:Cimetidine; D011899:Ranitidine; D009195:Peroxidase; D019342:Acetic Acid; D007213:Indomethacin