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Evaluation of Circadian Rhythm Disturbances in Mice Models with Impaired Heme Biosynthesis Induced by Environmental Chemicals

Research Project

Project/Area Number 18590119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionJosai International University

Principal Investigator

MITSUMOTO Atsushi  Josai International University, 薬学部, 教授 (00276164)

Co-Investigator(Kenkyū-buntansha) SATOH Yoko  城西国際大学, 薬学部, 助手 (90348178)
Co-Investigator(Renkei-kenkyūsha) KAWAI Hiroshi  城西国際大学, 薬学部, 講師 (20321854)
ISHIBASHI Takuya  城西国際大学, 薬学部, 助手 (20555825)
Research Collaborator WATANABE Yukino  城西大学, 大学院・薬学研究科
IWADATE Reiko  慶應義塾大学, 大学院・薬学研究科
Project Period (FY) 2006 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,190,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥690,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords概日リズム / 生物時計 / ポルフィリン症 / ヘム / 環境化学物質 / 肝障害 / グリセオフルビン / 疾病モデル動物 / 環境衛生学
Research Abstract

We have developed a mouse model of hepatic porphyria induced by ingestion of a chemical substance, griseofulvin (GF), and analyzed the characterization of biochemical and behavioral phenotypes of the porphyria model mice. The porphyria mice exhibited tremendous accumulation of aminolevurinic acid (ALA) and porphyrins asn heme precursors, and also had symptoms, such as liver injury and skin inflammation. In addition, they exhibited several neurological and psychological behaviors, such as anxiety and depression, typically observed in acute porphyria. Moreover, we found that these mice had differential sensitivities to psychological drugs, such as diazepam, comparing to the control mice, without any difference in the pharmacokinetics. Furthermore, circadian activity and temperature rhythms of these mice exhibited phase-advances by a few hours. The abnormal circadian rhythms were ameliorated by the treatment of heme. In conclusion, we demonstrated heme-regulated abnormality of circadian rhythms in the mice model of hepatic porphyria induced by GF.

Report

(6 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report   Self-evaluation Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (42 results)

All 2010 2009 2008 2007 2006 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (24 results) Remarks (2 results)

  • [Journal Article] Peroxisome proliferators attenuate free arachidonic acid pool in the kidney through inducing lysophospholipid acyltransferases.2009

    • Author(s)
      Yamazaki T, Hirose A, Sakamoto T, Okazaki M, Mitsumoto A, Kudo N, Kawashima Y
    • Journal Title

      J Pharmacol Sci 111(2)

      Pages: 201-10

    • NAID

      10025739242

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of reactive oxygen species in TGF-beta1-induced tropoelastin expression by human dermal fibroblasts.2009

    • Author(s)
      Choi WS, Mitsumoto A, Kochevar IE
    • Journal Title

      Photochem Photobiol 85(6)

      Pages: 1425-33

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats.2009

    • Author(s)
      Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      J Toxicol Sci 34(1)

      Pages: 27-38

    • NAID

      110007043225

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Peroxisome proliferators attenuate free arachidonic acid pool in the kidney through inducing lysophospholipid acyltransferases.2009

    • Author(s)
      Yamazaki T, Hirose A, Sakamoto T, Okazaki M, Mitsumoto A, Kudo N, Kawashima Y.
    • Journal Title

      J Pharmacol Sci. 111

      Pages: 201-10

    • NAID

      10025739242

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of reactive oxygen species in TGF-betal-induced tropoelastin expression by human dermal fibroblasts.2009

    • Author(s)
      Choi WS, Mitsumoto A, Kochevar IE.
    • Journal Title

      Photochem Photobiol. 85

      Pages: 1425-33

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats2009

    • Author(s)
      Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      J Toxicol Sci 34

      Pages: 27-38

    • NAID

      110007043225

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats.2009

    • Author(s)
      Kawai H, Kudo N, Kawashima Y, Mitsumoto A.
    • Journal Title

      J Toxicol Sci. 34

      Pages: 27-38

    • NAID

      110007043225

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria.2008

    • Author(s)
      Satoh Y, Iwadate R, Watanabe Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      J Toxicol Sci 33(5)

      Pages: 599-608

    • NAID

      110007005559

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria2008

    • Author(s)
      Satoh Y, Iwadate R, Watanabe Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      J Toxicol Sci 33

      Pages: 599-608

    • NAID

      110007005559

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic por2008

    • Author(s)
      Satoh Y, Iwadate R. Watanabe Y, Kawai H. Kudo N. Kawashima Y
    • Journal Title

      J Toxicol Sci. 33

      Pages: 599-608

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2007

    • Journal Title

      J.Health Sci. 53suppl

      Pages: 237-237

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Temperature rhythm reentrains faster than locomotor rhythm after a light phase shift.2006

    • Author(s)
      atoh Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      Physiol Behav 88(4-5)

      Pages: 404-10

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Time-restricted feeding entrains daily rhythms of energy metabolism in mice.2006

    • Author(s)
      Satoh Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol 290(5)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Temperature rhythm reentrains faster than locomotor rhythm after a light phase shift2006

    • Author(s)
      Satoh Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      Physiol Behav 88

      Pages: 404-10

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Time-restricted feeding entrains daily rhythms of energy metabolism in mice2006

    • Author(s)
      Satoh Y, Kawai H, Kudo N, Kawashima Y, Mitsumoto A
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol 290

      Pages: 1276-83

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] グリセオフルビン誘発ポルフィリアモデルマウスにおける運動機能障害2006

    • Author(s)
      佐藤陽子, 河合洋, 光本篤史
    • Journal Title

      J. Health Sci. 52(suppl)

      Pages: 238-238

    • Related Report
      2006 Annual Research Report
  • [Presentation] ポルフィリン症モデルマウスにおける薬物感受性の差異とGABA_A受容体の関連について2010

    • Author(s)
      光本篤史、渡邉ゆきの, ほか
    • Organizer
      日本薬学会年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] ポルフィリン症モデルマウスにおける薬物感受性の差異とGABAA受容体の関連について2010

    • Author(s)
      渡邉ゆきの、佐藤陽子、石橋拓也、河合洋、光本篤史
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2009 Final Research Report
  • [Presentation] Decreased Hypnotic Effects of GABAA-R Modulators on Hepatic Porphyria Mice2009

    • Author(s)
      渡邉ゆきの、光本篤史, ほか
    • Organizer
      国際睡眠学会第16回日本時間生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] Phase-advances of Circadian Rhythms in Mice with Impairment of Heme Biosynthesis.2009

    • Author(s)
      岩舘怜子、光本篤史, ほか
    • Organizer
      国際睡眠学会第16回日本時間生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヘム代謝異常と概日リズム障害2009

    • Author(s)
      光本篤史
    • Organizer
      日本薬学会関東支部大会
    • Place of Presentation
      城西大学(埼玉県坂戸市)
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヘム代謝異常と概日リズム障害2009

    • Author(s)
      光本篤史
    • Organizer
      日本薬学会関東支部大会
    • Place of Presentation
      坂戸
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝性ポルフィリン症マウスにおけるGABAA受容体モジュレーターによる催眠作用の低下2009

    • Author(s)
      渡邉ゆきの、佐藤陽子、石橋拓也、河合洋、光本篤史
    • Organizer
      第6回アジア睡眠学会・日本睡眠学会第34回定期学術集会・第16回日本時間生物学会学術大会
    • Place of Presentation
      大阪
    • Related Report
      2009 Final Research Report
  • [Presentation] ヘム代謝異常マウスにおける概日リズム障害2009

    • Author(s)
      岩舘怜子、佐藤陽子、石橋拓也、河合洋、増野匡彦、光本篤史
    • Organizer
      第6回アジア睡眠学会・日本睡眠学会第34回定期学術集会・第16回日本時間生物学会
    • Place of Presentation
      大阪
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝性ポルフィリン症マウスにおけるジアゼパムに対する感受性の差異2009

    • Author(s)
      渡邉ゆきの、河合洋、光本篤史
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report 2008 Annual Research Report 2008 Self-evaluation Report
  • [Presentation] Differential Response of Hepatic Porphyria Mice to Administration of Diazepam.2008

    • Author(s)
      Atsushi MITSUMOTO, Yukino WATANABE, Hiroshi KAWAI
    • Organizer
      第8回国際ポルフィリン・ヘムシンポジウム
    • Place of Presentation
      松江
    • Related Report
      2009 Final Research Report
  • [Presentation] Differential Response of Hepatic Porphyria Mice to Administration of Diazepam2008

    • Author(s)
      光本篤史、渡辺ゆきの、河合洋
    • Organizer
      第8回国際ポルフィリン・ヘムシンポジウム
    • Place of Presentation
      松江
    • Related Report
      2008 Annual Research Report 2008 Self-evaluation Report
  • [Presentation] 薬物誘発肝障害モデルラットにおける血清マーカーと尿中胆汁酸量の相関の解析2008

    • Author(s)
      河合洋、光本篤史
    • Organizer
      環境トキシコロジー2008
    • Place of Presentation
      熊本
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] 薬物誘発肝障害モデルラットにおける尿中胆汁酸量の測定2008

    • Author(s)
      河合洋、光本篤史
    • Organizer
      第128回日本薬学会年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] ポルフィリン症モデルマウスにおける行動異常2007

    • Author(s)
      佐藤 陽子, 河合 洋, 光本 篤史
    • Organizer
      衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pathophysiological Charactehzation in Griseofulvin-induced Porphyria Mice2007

    • Author(s)
      佐藤 陽子, 河合 洋, 光本 篤史
    • Organizer
      8th International ISSX Meeting
    • Place of Presentation
      仙台
    • Year and Date
      2007-10-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] ポルフィリン症モデルマウスにおける行動異常2007

    • Author(s)
      佐藤陽子, 河合洋, 光本篤史
    • Organizer
      フォーラム2007・衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Related Report
      2009 Final Research Report
  • [Presentation] Pathophysiologic characterization in Griseofulvin-induced porphyria mice.2007

    • Author(s)
      Yoko Satoh, Hiroshi Kawai, Atsushi Mitsumoto
    • Organizer
      8th ISSX
    • Place of Presentation
      仙台
    • Related Report
      2009 Final Research Report
  • [Presentation] ポルフィリン症モデルマウスにおける肝機能変化と運動機能障害2007

    • Author(s)
      佐藤陽子、河合洋、光本篤史
    • Organizer
      日本薬学会第127年会
    • Place of Presentation
      富山
    • Related Report
      2009 Final Research Report
  • [Presentation] ポルフィリン症モデルマウスにおける行動異常2007

    • Author(s)
      佐藤陽子、河合洋、光本篤史
    • Organizer
      フォーラム2007 : 衛生薬学・環境トキシコロジー
    • Place of Presentation
      大阪
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] Pathophysiological Characterization in Griseofulvin-induced Porphyria Mice2007

    • Author(s)
      光本篤史、佐藤陽子、河合洋
    • Organizer
      8th International ISSX Meeting
    • Place of Presentation
      仙台
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] 急性肝炎ラットにおける運動機能障害の定量的評価2007

    • Author(s)
      河合洋、光本篤史
    • Organizer
      第34回日本トキシコロジー学会
    • Place of Presentation
      東京
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] ポルフィリン症モデルマウスにおける肝機能変化と運動機能障害2007

    • Author(s)
      光本篤史、佐藤陽子、河合洋
    • Organizer
      第127回日本薬学会
    • Place of Presentation
      富山
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] グリセオフルビン誘発ポルフィリアモデルマウスにおける運動機能障害2006

    • Author(s)
      佐藤陽子、河合洋、光本篤史
    • Organizer
      フォーラム2006・衛生薬学・環境トキシコロジーシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] グリセオフルビン誘発ポルフィリアモデルマウスにおける運動機能障害2006

    • Author(s)
      光本篤史、佐藤陽子
    • Organizer
      フォーラム2006 : 衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京
    • Related Report
      2008 Self-evaluation Report
  • [Remarks] ホームページ等

    • URL

      http://www.jiu.ac.jp/pharmacy/faculty/index.html#name17

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.jiu.ac.jp/faculty/pc/eisei.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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