Leukotrienes as mediators in frog virus 3-induced hepatitis in rats.
The role of leukotrienes was investigated in frog virus 3-induced hepatitis in rats. Frog virus 3 elicited an enhanced generation of cysteinyl leukotrienes in vivo as monitored by measurement of N-acetyl-leukotriene E4 as the major endogenous metabolite of cysteinyl leukotrienes secreted into rat bile. N-Acetyl-leukotriene E4 concentrations were elevated for more than 4 hr after frog virus 3 injection. In vitro experiments using cultured rat liver Kupffer cells of high purity indicated that these cells can produce and metabolize leukotrienes and are thus a possible source of leukotrienes elicited in vivo by frog virus 3. The selective 5-lipoxygenase inhibitor AA 861 and the dual inhibitor of arachidonate lipoxygenase and cyclooxygenase, BW 755C, reduced the hepatocellular injury after a high dose of frog virus 3 by about 50 and 80%, respectively, as judged from plasma activities of ALT and sorbitol dehydrogenase at 24 hr after frog virus 3 administration. Our in vivo and in vitro studies argue in favor of an important role of leukotrienes as mediators in frog virus 3 hepatitis in rats.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016227:Benzoquinones; D001646:Bile / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000097:blood*; D007497:Iridoviridae / Q000472:pathogenicity; D007728:Kupffer Cells / Q000032:analysis; D017999:Leukotriene E4 / Q000031:analogs & derivatives*; D016859:Lipoxygenase Inhibitors; D008099:Liver / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains / Q000097:blood*; D012016:Reference Values; D013189:SRS-A / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood* / Q000378:metabolism
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D011809:Quinones; D013189:SRS-A; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D017999:Leukotriene E4; C047630:N-acetylleukotriene E4; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone