Nonessential role of leukotrienes as mediators of acute gastric mucosal injury induced by aspirin in rats.
The present study was designed to determine the role of leukotrienes in aspirin-induced acute gastric mucosal injury in rats. We examined the effects of aspirin, indomethacin, and sodium salicylate on gastric mucosal injury, and on eicosanoid synthesis and content. Aspirin, indomethacin, and acidified salicylate caused significant mucosal injury, while salicylate at pH 7 did not induce significant injury. Aspirin and indomethacin significantly reduced mucosal prostaglandin synthesis and content. No significant changes in mucosal leukotriene C4 synthesis and content were observed. There were no correlations between changes in mucosal leukotriene B4 synthesis and the extent of mucosal injury. We also evaluated the effects of MK-571 (a leukotriene D4 receptor antagonist) and MK-886 (a leukotriene biosynthesis inhibitor) on aspirin-induced gastric mucosal injury. Neither MK-571 nor MK-886 could reduce the mucosal lesions induced by aspirin. These findings suggest that leukotrienes are not involved in aspirin-induced acute gastric mucosal injury in rats.
Lee
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Feldman
M
M
D000208:Acute Disease; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors; D012980:Sodium Salicylate / Q000494:pharmacology; D002722:Chlorobenzenes
D001241:Aspirin; D007211:Indoles; D007213:Indomethacin; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011422:Propionates; D011804:Quinolines; D013189:SRS-A; D012980:Sodium Salicylate; C060893:MK-886; D002722:Chlorobenzenes; C059141:verlukast