Effect of OKY-046 and ONO-3708 on liver injury in mice.
The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5, 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Aoki
M
M
Shimazawa
T
T
Yakuo
I
I
Koda
A
A
Kasahara
M
M
D000179:Acrylates / Q000627:therapeutic use*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011464:Epoprostenol / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D008689:Methacrylates; D013928:Thromboxane A2; C049855:ONO 3708; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel; D007213:Indomethacin