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2007 Fiscal Year Final Research Report Summary

Molecular pathological analysis of pathogenesis of non-alcoholic steatohepatitis: Propose of new treatment approach

Research Project

Project/Area Number 18590324
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionUniversity of Toyama

Principal Investigator

TSUNEYAMA Koichi  University of Toyama, Graduate School of Medical and Pharmaceutical Science, Associate Professor (10293341)

Co-Investigator(Kenkyū-buntansha) TAKENO Yasuo  University of Toyama, Graduate School of Medical and Pharmaceutical Science, Professor (60142022)
Project Period (FY) 2006 – 2007
KeywordsNASH / animal model / oxidative stress / glycation / herval medicine
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.

  • Research Products

    (29 results)

All 2008 2007 2006 Other

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (12 results) Remarks (1 results)

  • [Journal Article] Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative NDA damage in nonalcoholic fatty liver disease.2008

    • Author(s)
      Nomoto K, et. al.
    • Journal Title

      Appl Immunohistochem Mol Morphol. 16(1)

      Pages: 71-75

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Monosodium glutamate(MSG): a villain and promoter of liver inflamma tion and dysplasia.2008

    • Author(s)
      Nakanishi Y, et. al.
    • Journal Title

      J Autoimmunity 30(1-2)

      Pages: 42-50

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A possible rat model for non-alcoholic steatohepatitis: Histological findings in SHR/NDmcr-cp rats.2008

    • Author(s)
      Kato S, et. al.
    • Journal Title

      Hepatol Res. 38(7)

      Pages: 743-744

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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 S-D Rats.2008

    • Author(s)
      Omagari K, et. al.
    • Journal Title

      Dig Dis Sci. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice.2008

    • Author(s)
      Nakanishi Y, et. al.
    • Journal Title

      Hepatol Res. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver.2008

    • Author(s)
      Fujimoto M, et. al.
    • Journal Title

      Exp Biol Med(Maywood). 233(3)

      Pages: 328-337

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Cytoplasmic fine granular expression of 8-hydroxydeoxy guanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease2008

    • Author(s)
      Nomoto, K., Tsuneyama, K., Takahashi, H., Murai, Y., Takano, Y
    • Journal Title

      Appl Immunohi stochem Mol Morphol 16(1)

      Pages: 71-5

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      Hepatol Res (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      J Autoimmun 30(1-2)

      Pages: 42-50

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      Hepatol Res 38(7)

      Pages: 743-4

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      Dig Dis Sci

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • 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
  • [Journal Article] Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis.2006

    • Author(s)
      Kainuma M, et. al.
    • Journal Title

      J Gastroenterol. 41(10)

      Pages: 971-980

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.2006

    • Author(s)
      Nomoto K, et. al.
    • Journal Title

      J Pathol. 210(4)

      Pages: 469-477

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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
    • Journal Title

      J Gastroenterol 41(10)

      Pages: 971-80

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Journal Title

      J Pathol 210(4)

      Pages: 469-77

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Year and Date
      20080423-27
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Evidence-Based Efficacy of Kampo Formulas on Liver Pathology in a Rabbit Model of Non Alcoholic Fatty Liver Disease.2007

    • Author(s)
      Fujimoto M, et. al.
    • Organizer
      The 14th International Congress of Oriental Medicine
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      20071200
    • Description
      「研究成果報告書概要(和文)」より
  • [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 Steatohepatitis.2007

    • Author(s)
      Fujimoto M, et. al.
    • Organizer
      The 58th Annual Meeting of The American Association for The Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Year and Date
      20071100
    • Description
      「研究成果報告書概要(和文)」より
  • [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
    • Year and Date
      20071100
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Japanese Herbal Medicines in the Prevention of Hepatic Fibrosis in NAFLD2007

    • Author(s)
      Fujimoto M, et. al.
    • Organizer
      The United States and Canadian Academy of Pathology, annual meeting 2007
    • Place of Presentation
      San Diego, USA
    • Year and Date
      20070300
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 非アルコール性脂肪性肝障害(NAFLD)の病態解析と漢方方剤の効果・新規モデル動物を用いた検討.2007

    • Author(s)
      常山幸一
    • Organizer
      富山大学21世紀COEプログラムシンポジウム「東洋の知に立脚した個の医療の創生」
    • Place of Presentation
      富山
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Strategy of future food science and food business.2007

    • Author(s)
      Tsuneyama K.
    • Organizer
      21st COE seminar "Integrate of New lnsights between Western and Eastern Medicines"
    • Place of Presentation
      Davis, USA
    • Year and Date
      2007-08-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] メタボリックシンドロームモデル動物に出現する非アルコール性脂肪性肝障害(NAFLD)の病理学的特徴2007

    • Author(s)
      常山幸一
    • Organizer
      第3回TSOD(肥満・糖尿病)マウス研究会情報交換会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 病理医からみたメタボリックシンドローム2007

    • Author(s)
      常山幸一
    • Organizer
      富山大学公開講座、「知っ得?納得!メタボリックシンドローム」
    • Place of Presentation
      富山
    • Year and Date
      2007-08-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 非アルコール性脂肪性肝障害モデルの病態解析と漢方方剤の効果-コレステロール負荷ウサギを用いた検討-2006

    • Author(s)
      常山幸一
    • Organizer
      北里大学21世紀COEプログラム・富山大学21世紀COEプログラム「天然資源からの抗感染症薬と病態制御へのアプローチ-東洋の知と生命科学の融合-」
    • Place of Presentation
      東京
    • Year and Date
      20061100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Disrupted galectin-3 causes nonalcoholic fatty liver disease in mice.2006

    • Author(s)
      Tsuneyama K, et. al.
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      20060600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Disrupted galectin-3 causes nonalcoholic fatty liver disease in mice2006

    • Author(s)
      Tsuneyama, K., Nomoto, K., Kato, I., Hiraga, K., Takano, Y
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      20060600
    • Description
      「研究成果報告書概要(欧文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.med.u-toyama.ac.jp/dpathol/index.html

URL: 

Published: 2010-02-04  

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