Leukotrienes in the pathogenesis of NSAID-induced gastric and intestinal mucosal damage.
Studies in pigs and rats were undertaken to explore further the role of leukotrienes following administration of NSAIDs on the development of gastrointestinal damage. Increased leukotriene C4 production occurred in the gastric circulation in the early stages after administration of a single dose of indomethacin (10 mg/kg i.g.) to pigs. Gastric and intestinal mucosal lesions by NSAIDs were prevented by both prior (2-5 h)+ 0.25 or 0h oral dosing of the 5-lipoxygenase inhibitor, MK-886, but not when only one of these doses was given. These results show the importance of enhanced peptidoleukotriene production in relation to microvascular damage from cyclooxygenase inhibition by NSAIDs.
Rainsford
K D
KD
Department of Biomedical Sciences, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada.
D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000188:drug therapy; D001241:Aspirin / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000633:toxicity*; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects*; D020024:Leukotriene Antagonists; D017997:Leukotriene C4 / Q000097:blood*; D016859:Lipoxygenase Inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D013270:Stomach / Q000098:blood supply; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control; D013552:Swine; D002722:Chlorobenzenes
D001241:Aspirin; D007211:Indoles; D007213:Indomethacin; D020024:Leukotriene Antagonists; D017997:Leukotriene C4; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes