Role of peptide-leukotrienes in liver injury in mice.
The role of peptide leukotrienes (p-LTs), especially LTC4 and LTD4 in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated mice. Carbon tetrachloride (CCl4)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC4 in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxygenase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC4 or LTD4 was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Shimazawa
T
T
Yakuo
I
I
Aoki
M
M
Koda
A
A
Kasahara
M
M
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D012898:Autacoids / Q000037:antagonists & inhibitors; D016227:Benzoquinones; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D015289:Leukotrienes / Q000502:physiology*; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D012898:Autacoids; D016227:Benzoquinones; D015289:Leukotrienes; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D010455:Peptides; D011809:Quinones; D013189:SRS-A; D013777:Tetrazoles; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C044660:LY 171883; D002251:Carbon Tetrachloride