Estimation of fetotoxicity of chemical compounds with human fetal liver cells and molecular basis of their toxicities

• Project/Area Number: 25460167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Shinshu University
• Principal Investigator: YAMAORI Satoshi 信州大学, 学術研究院医学系(医学部附属病院), 准教授 (40360218)
• Co-Investigator(Kenkyū-buntansha): OHMORI Shigeru 信州大学, 学術研究院医学系(医学部附属病院), 教授 (70169069)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ヒト胎児肝細胞 / 胎児毒性 / 薬物代謝酵素 / 発現解析

Outline of Final Research Achievements

Fetotoxicity of chemical compounds was investigated with human fetal liver cells. Among the chemical compounds examined, tamoxifen, diclofenac, and retinoic acid induced strong cytotoxicity, from which glutathione S-transferase did not protect human fetal liver cells. A lot of test compounds induced the expression of drug-metabolizing enzymes such as cytochrome P450s and sulfotransferases in human fetal liver cells.

Research Products

• [Journal Article] 切迫早産治療薬としてニフェジピンが奏功した一例 (2016)
  • Author(s): 小澤秀介, 小林愛子, 高津亜希子, 神田博仁, 山折 大, 塩沢丹里, 大森 栄
  • Journal Title: 医療薬学 Volume: 42 Pages: 202-208
  • NAID: 130005440106
  • Peer Reviewed
• [Journal Article] Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells (2015)
  • Author(s): Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K
  • Journal Title: Life Sci. Volume: 136 Pages: 87-93
  • DOI: 10.1016/j.lfs.2015.07.007
  • NAID: 120007100188
  • Peer Reviewed / Open Access
• [Journal Article] <i>In Vitro</i> Inhibition of CYP2C9-Mediated Warfarin 7-Hydroxylation by Iguratimod (2015)
  • Author(s): Yamaori S, Takami K, Shiozawa A, Sakuyama K, Matsuzawa N, Ohmori S
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 3 Pages: 441-447
  • DOI: 10.1248/bpb.b14-00711
  • NAID: 130004872267
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol (2014)
  • Author(s): Yamaori S, Okushima Y, Yamamoto I, Watanabe K
  • Journal Title: Chem. Biol. Interact. Volume: 215 Pages: 62-68
  • DOI: 10.1016/j.cbi.2014.03.007
  • NAID: 120007100189
  • Peer Reviewed
• [Presentation] エパルレスタットによるCYP4A11の選択的阻害作用 (2015)
  • Author(s): 山折 大, 荒木規行, 池畑くるみ, 大森 栄, 渡辺和人
  • Organizer: 日本薬物動態学会第30回年会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2015-11-12
• [Presentation] Potency and mechanism of CYP2J2 inhibition by major phytocannabinoids (2015)
  • Author(s): Yamaori S, Nagata Y, Ohmori S, Yamamoto I, Watanabe K
  • Organizer: 20th North American ISSX Meeting
  • Place of Presentation: Orlando (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Metabolism of major phytocannabinoids by human placenta microsomes and CYP19 (2015)
  • Author(s): Watanabe K, Inoue K, Murai M, Usami N, Yamaori S, Yamamoto I
  • Organizer: The 53rd Annual Meeting of the International Association of Forensic Toxicologists
  • Place of Presentation: Florence (Italy)
  • Year and Date: 2015-08-31
  • Int'l Joint Research
• [Presentation] Inducibility of CYP enzymes by cannabidiol (2015)
  • Author(s): Watanabe K, Yamaori S, Jiang R, Kinugasa Y, Okushima Y, Yamamoto I
  • Organizer: 25th Annual Symposium of the International Cannabinoid Research Society
  • Place of Presentation: Wolfville (Canada)
  • Year and Date: 2015-06-29
  • Int'l Joint Research
• [Presentation] Evaluation of Luciferin-4A O-demethylase activity as a CYP4A11 marker in human liver and kidney microsomes (2014)
  • Author(s): Yamaori S, Shionoiri M, Ohmori S, Watanabe K
  • Organizer: 19th North American ISSX Meeting and 29th JSSX Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-10-20
• [Presentation] ダナゾールのヒトCYP3A活性に対する阻害作用 (2014)
  • Author(s): 山折 大，津田有加，大森 栄，渡辺和人
  • Organizer: 医療薬学フォーラム2014／第22回クリニカルファーマシーシンポジウム
  • Place of Presentation: ビッグサイトTFTホール
  • Year and Date: 2014-06-29