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 bi...

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Published in:Hepatology (Baltimore, Md.) Md.), 1987-07, Vol.7 (4), p.732-736
Main Authors: HAGMANN, W, STEFFAN, A.-M, KIRN, A, KEPPLER, D
Format: Article
Language:English
Subjects:
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
Animal viral diseases
Animals
Benzoquinones
Bile - analysis
Biological and medical sciences
Cells, Cultured
Female
Hepatitis, Viral, Animal - blood
Infectious diseases
Iridoviridae - pathogenicity
Kupffer Cells - analysis
Leukotriene E4 - analogs & derivatives
Lipoxygenase Inhibitors
Liver - drug effects
Medical sciences
Pyrazoles - pharmacology
Quinones - pharmacology
Rats
Rats, Inbred Strains - blood
Reference Values
SRS-A - analogs & derivatives
SRS-A - analysis
SRS-A - blood
SRS-A - metabolism
Viral diseases
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Summary: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.
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.1840070419