Role of Thromboxane A_2 in Healing of Gastric Ulcers in Rats

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Author(s)

Abstract

We investigated the role of thromboxane (TX) A<SUB>2</SUB> in gastric ulcer healing in rats. Acetic acid ulcers were produced in male Donryu rats. TXA<SUB>2</SUB> synthesis in the stomachs with ulcers was significantly elevated in ulcerated tissue, but not in intact tissue, compared with that in the gastric mucosa of normal rats. Indomethacin inhibited both TXA<SUB>2</SUB> and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) synthesis in ulcerated tissue, while NS-398 (selective cyclooxygenase-2 inhibitor) reduced only PGE<SUB>2</SUB> synthesis. OKY-046 (TXA<SUB>2</SUB> synthase inhibitor) dose-relatedly inhibited only TXA<SUB>2</SUB> synthesis. The maximal effect of OKY-046 (80% inhibition) was found at more than 30 mg/kg. When OKY-046 was administered for 14 days, the drug at more than 30 mg/kg significantly accelerated ulcer healing without affecting acid secretion. The maximal reduction of ulcerated area by OKY-046 was about 30%, compared with the area in the control. Histological studies revealed that regeneration of the mucosa was significantly promoted by OKY-046, but neither maturation of the ulcer base nor angiogenesis in the base were affected. OKY-046 and TXB<SUB>2</SUB> had no effect on proliferation of cultured rat gastric epithelial cells, but U-46619 (TXA<SUB>2</SUB> mimetic) dose-relatedly prevented the proliferation without reducing cell viability. These results indicate that the increased TXA<SUB>2</SUB>, probably derived from cyclooxygenase-1 in ulcerated tissue, exerts a weak inhibitory effect on ulcer healing in rats. The effect of TXA<SUB>2</SUB> might be due partly to prevention of gastric epithelial cell proliferation at the ulcer margin.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(1), 101-107, 1999-01

    The Japanese Pharmacological Society

References:  26

Codes

  • NII Article ID (NAID)
    10008194293
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4636963
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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