Beneficial effect of 4-methylumbelliferone against bile duct ligation-induced hepatic fibrosis in rats
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- Sawada Naoya
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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- Mikami Kenichiro
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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- Igarashi Go
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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- Endo Tetsu
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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- Sato Ken
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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- Kakizaki Ikuko
- Department of Glycotechnology, Hirosaki University Graduate School of Medicine
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- Fukuda Shinsaku
- Department of Gastroenterology and Hematology, Hirosaki Graduate School of Medicine
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Abstract
Background & Aims: Liver fibrosis progresses to cirrhosis as the consequence of chronic liver injury. 4-methylumbelliferone (4-MU), a derivative of coumarin, has been used as an approved drug to treat biliary spasm. Recent publications have reported that 4-MU inhibits production of hyaluronan (HA), which is a key component of extracellular matrix deposition in fibrotic and cirrhotic liver. We investigated the effect of 4-MU on fibrotic liver in rats.<br> Methods: Liver fibrosis was induced by bile duct ligation (BDL). Male Sprague-Dawley rats received a standard diet or the same diet containing 1% or 5% of 4-MU from 1 week before BDL. The rats were sacrificed at 3 weeks after BDL.<br> Results: Administration of 4-MU increased serum 4-MU concentration levels, thereby decreasing serum HA levels in a dose-dependent manner. 4-MU treatment suppressed liver fibrosis in interlobular and pericentral areas with reduced alpha-smooth muscle actin expression, which suggested hepatic stellate cell activation.<br> Conclusion: Treatment with 4-MU suppressed the experimental hepatic fibrosis accompanied by inhibition of HA production. Although further experimental studies are needed, 4-MU could protect against fibrogenesis and may be repurposed as a safe therapeutic application for hepatic fibrosis.
Journal
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- Hirosaki Medical Journal
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Hirosaki Medical Journal 66 (2-4), 143-151, 2016
Hirosaki University Graduate School of Medicine,Hirosaki Medical Society
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Details 詳細情報について
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- CRID
- 1390288215570630784
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- NII Article ID
- 130008046377
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- NII Book ID
- AN00211444
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- ISSN
- 24344656
- 04391721
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- HANDLE
- 10129/5810
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- NDL BIB ID
- 027278230
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- NDL
- CiNii Articles
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- Abstract License Flag
- Disallowed