Adenosine protects against indomethacin-induced gastric damage in rats


Bozkurt A., Yüksel M. , Haklar G. , Kurtel H. , Yeğen B. , Alican Y. İ.

DIGESTIVE DISEASES AND SCIENCES, vol.43, pp.1258-1263, 1998 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 43
  • Publication Date: 1998
  • Doi Number: 10.1023/a:1018859824926
  • Title of Journal : DIGESTIVE DISEASES AND SCIENCES
  • Page Numbers: pp.1258-1263
  • Keywords: adenosine, indomethacin, gastric injury, mucosal permeability, neutrophil, chemiluminescence, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, OXYGEN METABOLITE PRODUCTION, ACID-SECRETION, ULCER FORMATION, MUCOSAL, INHIBITION, RECEPTOR, NEUTROPHILS, ACTIVATION

Abstract

This study examines the putative gastroprotective effect of adenosine on indomethacin-induced gastric lesions and the possible mechanisms involved. After 24 hr of starvation, the rats were treated either with indomethacin (Indo; 25 mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously, three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue-associated myeloperoxidase (MPO) activity and protein oxidation were measured in gastric tissue samples. Formation of reactive oxygen species in gastric tissues was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other groups of rats, gastric mucosal permeability and gastric acid output were performed following the same treatment regimens. The gastric mucosal permeability was measured by determination of [Cr-51]EDTA clearance in a perfused stomach preparation and gastric acid secretion studies were performed following pylorus ligation. The lesion index, the increase in lucigenin-enhanced chemiluminescence, and the increase in gastric mucosal permeability in Indo-treated rats were reversed by Ado pretreatment. Ado pretreatment also prevented the increase in gastric acid output and gastric volume in Indo-treated rats. Thus, these findings implicate that exogenous adenosine has a protective role on indomethacin-induced gastric lesions, possibly by inhibiting gastric hyperacidity and reactive oxygen formation and by preventing disruption of the mucosal integrity.