Leukotrienes in mucosal damage and protection.
Exposure of the rat gastric mucosa to ethanol stimulates the generation of leukotriene (LTC4) and 15-hydroxyeicosatetraenoic acid, but not of thromboxanes and prostaglandins. Lipoxygenase activation is not found with other topical irritants or nonsteroidal anti-inflammatory drugs. A number of gastroprotective drugs dose-dependently inhibit the stimulatory action of ethanol on mucosal LTC4 formation closely parallel to their protective activity suggesting that ethanol-induced damage and activation of lipoxygenases may involve common targets which are simultaneously counteracted by certain types of protective agents. Selective inhibition of 5-lipoxygenase, however, does not confer protection against gastric mucosal damage caused by topical irritants or non-steroidal anti-inflammatory drugs. Thus, although leukotrienes may mediate certain reactions elicited by gastric ulcerogens such as submucosal venular constriction and mucosal microvascular engorgement, they do not appear to be major mediators of ulcerogen-induced tissue necrosis. The contribution of other products of the various pathways of arachidonic acid metabolism to gastric mucosal injury and the mechanism underlying the close interrelationship between protection and inhibition of LTC4 formation observed with certain compounds remains to be investigated.
Peskar
B M
BM
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, FRG.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000431:Ethanol; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013270:Stomach / Q000187:drug effects; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D000431:Ethanol