| Project/Area Number |
17591420
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
KATSURAMAKI Tadasi Sapporo Medical University, School of medicine, Associate professor, 医学部, 助教授 (50253993)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Koichi Sapporo Medical University, School of medicine, Professor, 医学部, 教授 (50136959)
MIZUGUCHI Touri Sapporo Medical University, School of medicine, Assistant professor, 医学部, 講師 (30347174)
KIMURA Yasutoshi Sapporo Medical University, School of medicine, Assistant professor, 医学部, 講師 (80311893)
NAGAYAMA Minoru Sapporo Medical University, School of medicine, Instructor, 医学部, 助手 (40398326)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | liver cirrhosis / fibrosis / nitric oxide / inducible nitric oxide synthase / 繊維化抑制療法 / 線維化 / 線維化抑制療法 |
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| Research Abstract |
Inducible nitric oxide synthase (iNOS) activity was significantly elevated in viral hepatitis, alcoholic cirrhosis, and cholestasis. however, there are few reports on the relationship between iNOS and cirrhosis. Here, we investigated the effects of a new iNOS inhibitor which has been developed for oral administration in an experimental rat liver cirrhosis model. A cirrhotic rat model was developed by long-term administration of thioacetamide (TAA) injections. FR260330, is a new, rationally designed, selective iNOS inhibitor that can be administered orally. After 12 weeks of treatment with FR260330, the rats showed inhibition of progressions of cirrhosis, ascites, and splenomegaly as well as a significant reduction in the proportions of connective tissue in the liver. The expression of nitrotyrosine, which indicates the existence of peroxynitrite and nuclear factor- kappa B (NFkB) activation, was remarkably decreased in the FR260330 treatment group. In addition, imnunohistochemical and western blot analyses showed that the expression of transforming growth factor beta-1 (TGFb1) was remarkably decreased in this group. The present study demonstrates that FR260330 reduces liver fibrosis by the inhibition of TGFb1 and retards the development of cirrhosis. This oral iNOS inhibitor will be a new strategy for the treatment of cirrhosis
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