Diethylcarbamazine decreases ethanol-injury to the gastric mucosa of the rat.
Exposure of the rat stomach to ethanol stimulates the generation of leukotrienes. Leukotrienes are potent mediators of tissue inflammation and injury. In this work we show that pretreatment with diethylcarbamazine, a lipoxygenase enzyme inhibitor, significantly decreases ethanol injury to the rat gastric mucosa. At a dose of 250 mg/kg the compound significantly reduced the ETOH-stimulated mucosal LTC4 generation by 40% and PGE2 generation by 79%. We conclude that diethylcarbamazine is an inhibitor of the cyclooxygenase and lipoxygenase enzymes in the gastric mucosa. That inhibition of leukotriene synthesis decreases the extent of ethanol-stimulated suggests that leukotrienes play a key role in mediating ethanol-injury to that tissue.
Balaa
M A
MA
Good Samaritan Medical Groups, San Jose, CA 94124.
Subramony
C
C
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004049:Diethylcarbamazine / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D015289:Leukotrienes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D000431:Ethanol; D015232:Dinoprostone; D004049:Diethylcarbamazine