The role of platelet activating factor [correction of actor] in acute gastric injury and its protection by sucralfate.
Platelet activating factor, a potent inflammatory mediator, has been reported to induce gastrointestinal damage, whereas its inhibition or antagonism is associated with mucosal protection. The aim of the present study was to elucidate the association between acute experimental gastric damage and mucosal platelet activating factor generation in the rat, and to evaluate the protective effect of sucralfate in relation to mucosal platelet activating factor formation. Gastric damage in the rat was induced by either subcutaneous injection of indomethacin 30 mg/kg or intragastric administration of aspirin 100 mg/kg, hydrochloric acid 0.6 N, taurocholate 30 mM, ethanol 96%, or sodium chloride 25%. All agents induced a significant increase in mucosal platelet activating factor levels concomitantly with induction of mucosal damage. Pretreatment with sucralfate 150 mg/rat provided a significant macroscopic and microscopic mucosal protection in all experimental models. This protection was associated with a significant decrease in mucosal platelet activating factor level in the hydrochloric acid, taurocholate, ethanol and hyperosmolar sodium chloride treated rats, whereas it remained unchanged in the aspirin and indomethacin treated rats. The data imply that platelet activating factor may have a limited role in the pathogenesis of indomethacin or aspirin induced damage, where other mechanisms such as cyclooxygenase inhibition dominate. In the damage induced by topical strong irritants, platelet activating factor may have a major pathogenetic role.
Ligumsky
M
M
Department of Gastroenterology, Hadassah University Hospital, Jerusalem, Israel.
Sestieri
M
M
Karmeli
F
F
Okon
E
E
Rachmilewitz
D
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005753:Gastric Mucosa / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D013276:Stomach Ulcer / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D013392:Sucralfate / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010972:Platelet Activating Factor; D013392:Sucralfate