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Enzymatic and metabolic adaptation to chronic alcohol consumption mediated by alcohol dehydrogenase 1 and 3 in mice.

Research Project

Project/Area Number 16K09223
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionNippon Medical School

Principal Investigator

Ohno Youkichi  日本医科大学, 大学院医学研究科, 大学院教授 (70152220)

Co-Investigator(Kenkyū-buntansha) 五十嵐 勉  日本医科大学, 医学部, 准教授 (10421190)
奥田 貴久  日本医科大学, 医学部, 准教授 (20620305)
Research Collaborator HASEBA takeshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアルコール脱水素酵素 / アルコール代謝 / 肝障害 / ADH3 / ADH1 / 慢性飲酒 / 社会医学 / 酵素
Outline of Final Research Achievements

We investigated the effects of ADH1 and ADH3 on alcoholic liver disease during chronic alcohol consumption (CAC) to clarify their involvement in ADH pathogenesis. Nine-week-old male mice of different ADH genotypes (WT, Adh1-/-, and Adh3-/-) were administered 10% ethanol solution for 1 month, followed by acute ethanol administration (4.0 g/kg). Blood alcohol concentration (BAC) was measured, and the alcohol elimination rate (AER) was calculated. The liver content was evaluated by ELISA. CAC increased AER in all ADH genotypes, indicating that the mice acquired metabolic tolerance to ethanol in the early period of CAC. The increased ADH1 content was correlated with AER in WT mice. Similarly, the increased ADH3 content was also correlated with AER in both WT and Adh1-/- mice. We conclude that ADH1 contributes to metabolic pharmacokinetics of CAC with increased AER by increasing the enzyme content3. ADH3 also contributes to increased AER by an adaptive increase in the enzyme content.

Academic Significance and Societal Importance of the Research Achievements

肝アルコール脱水素酵素では、ADH1・ADH3ともに代謝適応があり、慢性飲酒の初期には酵素量を増加させてアルコール代謝の亢進に寄与していることが示唆された。ADHを介したアルコール代謝では、ADH1のみならずADH3も慢性飲酒においても代謝耐性を獲得し、全身諸臓器でアルコール代謝に強く関与していると考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Funded Workshop (2 results)

  • [Journal Article] The Effect of Alcohol Dehydrogenase Isozymes on Alcoholic Liver Disease and Alcoholic Osteoporosis2019

    • Author(s)
      Okuda Takahisa
    • Journal Title

      Journal of Nippon Medical School

      Volume: 86 Issue: 1 Pages: 58-59

    • DOI

      10.1272/jnms.JNMS.2019_86-11

    • NAID

      130007620538

    • ISSN
      1345-4676, 1347-3409
    • Year and Date
      2019-01-15
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic pharmacokinetics of early chronic alcohol consumption mediated by liver alcohol dehydrogenases 1 and 3 in mice2018

    • Author(s)
      Okuda Takahisa、Haseba Takeshi、Katsuyama Midori、Maruyama Motoyo、Akimoto Toshio、Igarashi Tsutomu、Ohno Youkichi
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 33 Issue: 11 Pages: 1912-1919

    • DOI

      10.1111/jgh.14260

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Principles of fetal postmortem ultrasound: a personal review2016

    • Author(s)
      Okuda T, Shiotani S, Kobayashi T
    • Journal Title

      J Forensic Radilo Imaging.

      Volume: 5 Pages: 50-1

    • DOI

      10.1016/j.jofri.2016.04.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Enzymatic and metabolic adaptation to ethanol by alcohol dehydrogenase 1 and 3 in mice.2018

    • Author(s)
      T.Okuda et al.
    • Organizer
      24th Congress of International Academy of Legal Medicine (Fukuoka).
    • Related Report
      2018 Annual Research Report
  • [Presentation] 慢性アルコール摂取の骨に及ぼす影響とClassⅢアルコール脱水素酵素(ADH3)の役割2017

    • Author(s)
      奥田貴久、成尾宗弘、大野曜吉、長谷場健.
    • Organizer
      日本法医学学会
    • Related Report
      2017 Research-status Report
  • [Presentation] The role of Class III Alcohol Dehydrogenase (ADH3) in alcohol-related disorder on liver and bone.2017

    • Author(s)
      Okuda T, Maruyama M, Akimoto T, Ohno Y, Haseba T.
    • Organizer
      .2017 ESBRA Congres
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Funded Workshop] ISBRA20162016

    • Place of Presentation
      Berlin
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
  • [Funded Workshop] WAML20162016

    • Place of Presentation
      Los Angels
    • Year and Date
      2016-08-08
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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