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Elucidation of the mechanism for disease modulation by iron overload in chronic liver diseases

Research Project

Project/Area Number 17K08084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Veterinary medical science
Research InstitutionOsaka Prefecture University

Principal Investigator

Izawa Takeshi  大阪府立大学, 生命環境科学研究科, 准教授 (20580369)

Co-Investigator(Kenkyū-buntansha) 竹中 重雄  大阪府立大学, 総合リハビリテーション学研究科, 教授 (10280067)
桑村 充  大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords鉄過剰 / 慢性肝疾患 / 代謝性肝疾患 / 薬剤性肝傷害 / 肝硬変 / 肝障害 / マクロファージ / 炎症 / 酸化ストレス / 薬剤性肝障害
Outline of Final Research Achievements

The present study showed that experimental hepatic iron overload suppresses thioacetamide- or acetaminophen-induced liver injury and exacerbates allyl alcohol-induced liver injury, via changes in xenobiotic enzymes. It also showed that the hepatic iron overload also abrogates thioacetamide-induced liver cirrhosis, by suppression of hepatocellular apoptosis. The hepatic iron overload was shown to enhance high-fat diet-induced steatohepatitis, by excess activation of local lobular inflammation. The present study elucidated some mechanisms for the dual role in the modulation of liver diseases by iron overload.

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行によって,慢性肝疾患において,肝臓の鉄蓄積が時に病態を増悪し,時に抑制するという二面性を発揮するメカニズムの一端が解明された。慢性肝疾患の1つである非アルコール性脂肪性肝疾患は,国内の成人の約20~30%が罹患していると考えられており,肝臓の鉄蓄積はその3割程度にみられることが予測される。本研究で得られたデータが慢性肝疾患の病態解明の一助となることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The role of iron overload in the progression of nonalcoholic steatohepatitis (NASH)2019

    • Author(s)
      新 真智, 井澤 武史, 桑村 充, 山手 丈至
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 154 Issue: 2 Pages: 61-65

    • DOI

      10.1254/fpj.154.61

    • NAID

      130007689318

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dietary iron overload abrogates chemically-induced liver cirrhosis in rats.2018

    • Author(s)
      Atarashi M, Izawa T, Mori M, Inai Y, Kuwamura M, Yamate J
    • Journal Title

      Nutrients

      Volume: 10 Issue: 10 Pages: 1400-1400

    • DOI

      10.3390/nu10101400

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis2018

    • Author(s)
      Machi Atarashi、Takeshi Izawa、Rena Miyagi、Shoko Ohji、Ai Hashimoto、Mitsuru Kuwamura、Jyoji Yamate
    • Journal Title

      Nutrients

      Volume: 10 Issue: 2 Pages: 175-175

    • DOI

      10.3390/nu10020175

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 実験的鉄過剰による肝疾患の修飾多様性2019

    • Author(s)
      井澤 武史,新 真智,稲井 洋平,森 睦貴,桑村 充,山手 丈至
    • Organizer
      第43回日本鉄バイオサイエンス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝疾患(NAFLD)モデルラットにおける鉄過剰の病態修飾機序の解明2019

    • Author(s)
      藤原 咲春,井澤 武史,森 睦貴,新 真智,桑村 充,山手 丈至
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鉄過剰による化合物誘発性肝障害の部位特異的修飾メカニズムの解析2018

    • Author(s)
      森 睦貴,井澤武史,稲井洋平,新 真智,桑村 充,山手丈至
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of hemorrhagic diathesis in rats fed a high-iron diet2018

    • Author(s)
      Izawa T, Mori M, Atarashi M, Tsuchiya S, Kuwamura M, Yamate J
    • Organizer
      STP (Society of Toxicologic Pathology) 37th Annual Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 非アルコール性脂肪性肝炎モデルラットの肝炎進展に関わる全身免疫の役割2018

    • Author(s)
      井澤武史,大地祥子,新 真智,宮城伶奈,橋本 愛,桑村 充,山手丈至
    • Organizer
      第34回日本毒性病理学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高脂肪食誘発性肝疾患に対するラットの週齢感受性の解析2017

    • Author(s)
      大地祥子,稲井洋平,井澤武史,桑村 充,山手丈至
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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