Effect of OKY-046 and ONO-3708 on liver injury in mice.
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概要
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The effects of OKY-046, a selective thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>) synthetase inhibitor, and ONO-3708, a novel TXA<SUB>2</SUB> 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 lgG or by an injection of bacterial lipopolysaccharide (LPS) into <I>Corynebacterium parvum</I> (<I>C. parvum</I>) 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 I<SUB>2</SUB> 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.
- 公益社団法人 日本薬理学会の論文
著者
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YAKUO Ikuhisa
Department of Pharmacology, Gifu Pharmaceutical University
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Koda Akihide
Department Of Pharmacology Gifu College Of Pharmacy
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Yakuo Ikuhisa
Department Of Pharmacology Exploratory Research Laboratories Dainippon Pharmaceutical Co. Ltd.
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Kasahara Masao
Department Of Electronics And Information Science Faculty Of Engineering And Design Kyoto Institute
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Nagai Hiroichi
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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SHIMAZAWA Tsukasa
Department of Pharmacology, Gifu Pharmaceutical University
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AOKI Motonori
Department of Pharmacology, Gifu Pharmaceutical University
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