Adenosine protects against indomethacin-induced gastric damage in rats.
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 [51Cr]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.
Bozkurt
A
A
Department of Physiology, Marmara University, School of Medicine, Haydarpaşa, Istanbul, Turkey.
Yüksel
M
M
Haklar
G
G
Kurtel
H
H
Yeğen
B C
BC
Alican
I
I
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002463:Cell Membrane Permeability; D019610:Cytoprotection; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D007213:Indomethacin / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D009195:Peroxidase; D000241:Adenosine; D007213:Indomethacin