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

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Author(s)

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 H<SUB>2</SUB>-receptor antagonists (H<SUB>2</SUB>-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 mm<SUP>2</SUP>, 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 H<SUB>2</SUB>-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 H<SUB>2</SUB>-RAs act mainly on the process of aggravation.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 73(3), 229-241, 1997-03-01

    The Japanese Pharmacological Society

References:  38

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008677462
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4196918
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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