Aspirin-like drugs, ethanol-induced rat gastric injury and mucosal eicosanoid release.
The effect of oral administration of various non-steroidal antiinflammatory drugs on ethanol-induced rat gastric injury and mucosal release of leukotriene C4, 6-keto-prostaglandin F1 alpha and 15-hydroxy-5,8,11,13-eicosatetraenoic acid was investigated. It was found that besides sodium salicylate and high doses of aspirin, other salicylate-type drugs, such as diflunisal, 4-aminosalicylic acid, 2,4-dihydroxybenzoic acid and methyl salicylate, and several non-acidic compounds, such as proquazone, benzydamine and paracetamol, were gastroprotective. All these drugs inhibited ex vivo leukotriene C4 formation by ethanol-stimulated gastric mucosa. However, naproxen, lonazolac, ibuprofen, gentisic acid and 5-aminosalicylic acid also inhibited leukotriene C4 formation, but were not protective. Gastroprotection was independent of 6-keto-prostaglandin F1 alpha formation. Both protective and non-protective drugs inhibited the ethanol-stimulated, but not the basal, release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid. The results indicate that the differential effects of various non-steroidal antiinflammatory drugs on gastroprotection against ethanol are not correlated with specific effects on mucosal cyclooxygenase, 5-lipoxygenase or 15-lipoxygenase activity.
Trautmann
M
M
Department of Experimental Clinical Medicine, Ruhr-University, Bochum, F.R.G.
Peskar
B M
BM
Peskar
B A
BA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D013189:SRS-A; D000431:Ethanol; D015121:6-Ketoprostaglandin F1 alpha; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001241:Aspirin