Molecular pathological analysis of pathogenesis of non-alcoholic steatohepatitis: Propose of new treatment approach
| Project/Area Number |
18590324
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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 |
Human pathology
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| Research Institution | University of Toyama |
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Principal Investigator |
TSUNEYAMA Koichi University of Toyama, Graduate School of Medical and Pharmaceutical Science, Associate Professor (10293341)
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| Co-Investigator(Kenkyū-buntansha) |
TAKENO Yasuo University of Toyama, Graduate School of Medical and Pharmaceutical Science, Professor (60142022)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | NASH / animal model / oxidative stress / glycation / herval medicine / AGE / RAGE / ガレクチン3 |
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| Research Abstract |
Metabolic syndrome is one of the most important disease conditions in all over the world. Severe and incurable diseases such as diabetes mellitus, arteriosclerosis and cerebro-vascular diseases were induced from lipid overdeposition in visceral fat. Recently, hepatic manifestation of metabolic syndrome was noted as non-alcoholic fatty liver diseases (NAFLD). Especially, non alcoholic steatohepatitis (NASH), which is severe phenotype of NAFLD is of a serious concern due to its increasing prevalence in the westernized world. Importantly, NASH may ultimately lead to the development of liver cirrhosis and hepatocellular carcinoma even in young generation. To make clarify the disease mechanism of NAFLD under the condition of obesity, we developed several unique animal models based on different disease condition. High-cholesterol fed rat and rabbit showed typical slender fibrosis as well as lipid overload in the liver, similar to human liver fibrosis. While Galectin-3 knock out mice, monosodium-glutamate treated mice and SHR/NDmcr-cp rats showed central obese, type 2 diabetes and marked fatty change with inflammation in predominant to male. We analyzed these animals showing NASH-like liver pathology as well as human liver specimens suffering NASH. In present study, we succeeded to clarify that lipid peroxidation, oxidative stress and glycation play important roles for disease progress of NASH. In addition, we made clarify the preventional roles of NASH using several traditional herval medicines. To find the effective products for metabolic syndrome including NASH is one of the most important contribution for primary care of peoples candidate of metabolic syndrome. We will continue to seek some effective natural products using our animal models.
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Report
(3 results)
Research Products
(50 results)
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[Journal Article] Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice2008
Author(s)
Nakanishi, Y., Tsuneyama, K., Nomoto, K., Fujimoto, M., Salunga, TL., Nakajima, T., Miwa, S., Murai, Y., Hayashi, S., Kato, I., Hiraga, K., Hsu, DK., Liu, FT., Takano, Y
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Journal Title
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Monosodium glutamate(MSG): a villain and promoter of liver inflammation and dysplasia2008
Author(s)
Nakanishi, Y., Tsuneyama, K., Fujimoto, M., Salunga, TL., Nomoto, K., An, JL., Takano, Y., Iizuka, S., Nagata, M., Suzuki, W., Shimada, T., Aburada, M., Nakano, M., Selmi, C., Gershwin, ME
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Journal Title
J Autoimmun 30(1-2)
Pages: 42-50
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A possible rat model for non-alcoholic steatohepatitis: Histological findings in SHR/NDmcr-cp rats2008
Author(s)
Kato, S., Omagari, K., Tsuneyama, K., Fukazawa, E., Tsukuda, H., Inohara, C., Kuroda, Y., Shiraishi, K., Mune, M
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Journal Title
Hepatol Res 38(7)
Pages: 743-4
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of a Long-Term High-Fat Diet and Switching from a High-Fat to Low-Fat, Standard Diet on Hepatic Fat Accumulation in Sprague-Dawley Rats2008
Author(s)
Omagari, K., Kato, S., Tsuneyama, K., Inohara, C., Kuroda, Y., Tsukuda, H., Fukazawa, E., Shiraishi, K., Mune, M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver2008
Author(s)
Fujimoto, M., Tsuneyama, K., Kainuma, M., Sekiya, N., Goto, H., Takano, Y., Terasawa, K., Selmi, C., Gershwin, ME., Shimada, Y
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Journal Title
Exp Biol Med(Maywood) 233(3)
Pages: 328-37
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis2006
Author(s)
Kainuma, M., Fujimoto, M., Sekiya, N., Tsuneyama, K., Cheng, C., Takano, Y., Terasawa, K., Shimada, Y
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Journal Title
J Gastroenterol 41(10)
Pages: 971-80
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice2006
Author(s)
Nomoto, K., Tsuneyama, K., Abdel, Aziz, H0., Takahashi, H., Murai, Y., Cui, ZG., Fujimoto, M., Kato, I., Hiraga, K., Hsu, DK., Liu, FT., Takano, Y
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Journal Title
J Pathol 210(4)
Pages: 469-77
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Monosodium glutamate injection induces a new comprehensive model of lifestyle-related non alcoholic fatty liver disease with neoplastic nodules2008
Author(s)
Nakanishi, Y., Tsuneyama, K., Fujimoto, M., Salunga, TL., Nomoto, K., An, JL., Gershwin, ME
Organizer
43rd Annual Meeting of the European Association for the Study of the Liver(EASL)
Place of Presentation
Milan, Italy
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Traditional Japanese Kampo Formula keishibukuryogan Ameliorates Steatosis, Reduces Oxidative Stress and Inflammation and Ultimately Prevents Liver Fibrosis in a Rabbit Model of Non Alcoholic Steatohepatitis2007
Author(s)
Fujimoto, M., Tsuneyama, K., Kainuma, M., Sekiya, N., Goto, H., Takano, Y., Terasawa, K., Selmi, C., Gershwin, ME., Shimada, Y
Organizer
The 58th Annual Meeting of The American Association for The Study of Liver Diseases
Place of Presentation
Boston, USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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