The effects of thromboxane A2 inhibitors (OKY-046 and ONO-3708) and leukotriene inhibitors (AA-861 and LY-171883) on CCl4-induced chronic liver injury in mice.
The effects of OKY-046, a selective thromboxane A2 (TxA2) synthetase inhibitor, ONO-3708, a novel TxA2 receptor antagonist, AA-861, a selective 5-lipoxygenase inhibitor and LY-171883, a peptide leukotrienes (p-LTs) receptor antagonist on the chronic liver injury were investigated in mice. The chronic liver injury was induced by the injection of carbon tetrachloride (CCl4) two times a week for twelve weeks in mice. In chronic liver injury models, significant histopathological changes in the liver and extensive elevation of glutamate transaminase (GOT and GPT) activity were observed. Administration of OKY-046, ONO-3708, AA-861 and LY-171883 for 12 weeks suppressed the elevation of serum GOT and GPT levels and histopathological changes in CCl4-induced chronic liver injury. These results suggest that TxA2 and LTs inhibitors are effective for the onset and development of chronic liver injury in mice.
Shimazawa
T
T
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Nagai
H
H
Koda
A
A
Kasahara
M
M
D000098:Acetophenones / Q000494:pharmacology*; D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D016227:Benzoquinones; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D051379:Mice; D011809:Quinones / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000098:Acetophenones; D000179:Acrylates; D001393:Azoles; D016227:Benzoquinones; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D008689:Methacrylates; D011809:Quinones; D013777:Tetrazoles; D013928:Thromboxane A2; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C044660:LY 171883; C049855:ONO 3708; D013930:Thromboxane-A Synthase; C034364:ozagrel