Application of hydrogen water to develop new therapy for drug-induced gingival overgrowth

• Project/Area Number: 17K11685
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nihon University
• Principal Investigator: TAKEUCHI Reiri 日本大学, 松戸歯学部, 講師 (60419778)
• Co-Investigator(Kenkyū-buntansha): 有川 量崇 日本大学, 松戸歯学部, 教授 (50318325) ; 伊藤 耕 日本大学, 松戸歯学部, 講師 (20419758) ; 田口 千恵子 日本大学, 松戸歯学部, 助教 (80434091)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 薬物性歯肉増殖症 / ラット / 病態モデル / 歯肉線維芽細胞 / アポトーシス / 細胞増殖 / 細胞周期 / 水素水 / 炎症 / 動物モデル / 歯学 / 線維芽細胞

Outline of Final Research Achievements

The experiments using animals are beneficial to develop the new therapy using hydrogen water for the drug-induced gingival overgrowth. In this study, the effects of hydrogen water were investigated using rats induced the inflammation on the tongue. The hydrogen water showed the anti-inflammatory effect on the rat tongue through the decreased in the mRNA expression of interleukin 6. Also, the development of new therapy requires to investigate the mechanism of the drug-induced gingival overgrowth. In this study, it was showed that the mechanism of the phenytoin-induced gingival overgrowth was related to the reduction of the apoptosis in the gingival fibroblasts exposed to phenytoin. The results of the research contribute to develop the new therapy for the drug-induced gingival overgrowth, and also to investigate the mechanism of this disease.

Academic Significance and Societal Importance of the Research Achievements

水素水を応用した新規治療法の開発には、生体を丸ごと扱う動物実験で、生体内の複雑な生理機能に対する水素水の効果を評価することが必要である。本研究では、ラット舌に炎症を生じ、水素水がその炎症症状を緩解することを確認し、さらに、水素水の抗炎症作用の機序として、インターロイキン６等の炎症性因子発現が変化することも明らかになった。一方、治療のためには疾患の発症機序解明も必要である。本研究では、原因薬物の一つであるフェニトインが歯肉線維芽細胞アポトーシスを抑制することを明らかにした。研究成果は、本疾患の新たな治療法開発および発症機序の解明に寄与した。

Research Products

• [Journal Article] Mechanism of Drug-induced Gingival Overgrowth: Phenytoin Inhibits the Apoptosis of Human Gingival Fibroblasts (2021)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Chieko Taguchi, Yuichiro Okada, Masaru Mizuta, Takashi Yamada, Toru Aso, Haruka Sakazume, Kazumune Arikawa, Koichi Hiratsuka
  • Journal Title: International Journal of Oral-Medical Sciences Volume: 20 Issue: 2 Pages: 109-116
  • DOI: 10.5466/ijoms.20.109
  • NAID: 130008106166
  • ISSN: 1347-9733, 2185-4254
  • Year and Date: 2021-10-20
  • Peer Reviewed / Open Access
• [Journal Article] Anti-apoptotic Effects of Propofol on Akt/GSK3<i>β</i> Pathway and Intracellular pH in Alveolar Epithelial Cells (2021)
  • Author(s): Hiroko Matsumoto, Masatoshi Suzuki, Reiri Takeuchi, Koichi Hiratsuka, Hidenori Yamaguchi
  • Journal Title: International Journal of Oral-Medical Sciences Volume: 20 Issue: 2 Pages: 126-131
  • DOI: 10.5466/ijoms.20.126
  • NAID: 130008106183
  • ISSN: 1347-9733, 2185-4254
  • Year and Date: 2021-10-20
  • Peer Reviewed / Open Access
• [Journal Article] 水素水の抗炎症作用による口腔粘膜炎の予防効果の検討 (2018)
  • Author(s): 竹内麗理、有川量崇、田口千恵子、末光正昌、森川美雪、丸山満博、渡邉信幸、久山佳代、平塚浩一
  • Journal Title: 日大口腔科学 Volume: 44 Pages: 39-46
  • Peer Reviewed
• [Presentation] Basic study for establishment of stomatitis animal model (2021)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Koichi Hiratsuka
  • Organizer: 第63回歯科基礎医学会学術大会
• [Presentation] 口内炎の研究～ラット舌の炎症誘発とサイトカイン発現～ (2021)
  • Author(s): 竹内麗理, 田口千恵子, 末光正昌, 森川美雪, 松本裕子, 有川量崇, 久山佳代, 平塚浩一
  • Organizer: 第24回日本歯科医学会学術大会
• [Presentation] Fundamental study for establishment of oral mucositis animal model (2021)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Koichi Hiratsuka
  • Organizer: 第41回日本歯科薬物療法学会学術大会
• [Presentation] ラットによる口内炎の研究～舌への炎症誘発とインターロイキン発現～ (2021)
  • Author(s): 竹内麗理, 田口千恵子, 岡田優一郎, 中村茂, 水田勝, 山田孝, 麻生泰, 有川量崇, 平塚浩一
  • Organizer: 第70回日本口腔衛生学会・総会
• [Presentation] A new animal model for investigation of the oral mucositis disease (2020)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Koichi Hiratsuka
  • Organizer: 第62回歯科基礎医学会学術大会
• [Presentation] 口腔粘膜疾患モデルの開発 (2020)
  • Author(s): 竹内麗理, 田口千恵子, 末光正昌, 森川美雪, 松本裕子, 有川量崇, 久山佳代, 平塚浩一
  • Organizer: 第40回日本歯科薬物療法学会学術大会
• [Presentation] ラット舌への炎症誘発 (2020)
  • Author(s): 竹内麗理, 田口千恵子, 岡田優一郎, 岡田祐輔, 永岡明記, 中村茂, 李昌弘, 有川量崇, 平塚浩一
  • Organizer: 第69回日本口腔衛生学会・総会
• [Presentation] Effect of phenytoin on PI3K/Akt signaling pathway in human gingival fibroblasts (2020)
  • Author(s): Hiroko Matsumoto, Reiri Takeuchi, Junichi Yamane, Hitoshi Nishimura, Masamichi Komiya
  • Organizer: 第93回日本薬理学会年会
• [Presentation] Propofol reduces MAPK phosphorylation induced by interleukin-1β in HBSMCs (2019)
  • Author(s): Hiroko Matsumoto, Hidenori Yamaguchi, Reiri Takeuchi, Hitoshi Nishimura, Masamichi Komiya, Koh Shibutani
  • Organizer: 4th Meeting of the IADR Asia Pacific Region 2019
  • Int'l Joint Research
• [Presentation] Basic study on medication for gingival overgrowth (2019)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Chieko Taguchi, Akinobu Aoki, Kazumune Arikawa, Koichi Hiratsuka
  • Organizer: 97th General Session & Exhibition of the IADR
  • Int'l Joint Research
• [Presentation] ラットを用いた口腔粘膜の炎症性疾患モデル作製 (2019)
  • Author(s): 竹内麗理, 田口千恵子, 岡田祐輔, 永岡明記, 中村茂, 李昌弘, 岡田優一郎, 有川量崇, 平塚浩一
  • Organizer: 第68回日本口腔衛生学会・総会
• [Presentation] 18-alpha-glycyrrhetinic acid induced the apoptosis against PHT in the gingival fibroblasts (2019)
  • Author(s): Takeuchi R, Matsumoto H, Taguchi C, Ito K, Aoki A, Takahashi K, Arikawa K, Kondoh T, Hiratsuka K
  • Organizer: 第39回日本歯科薬物療法学会学術大会
• [Presentation] Cell cycle and apoptosis in gingival fibroblasts exposed to nifedipine (2018)
  • Author(s): Takeuchi R, Matsumoto H, Taguchi C, Arikawa K, Ito K, Aoki A, Takahashi K, Kondoh T, Hiratsuka K
  • Organizer: 18th WORLD CONGRESS OF BASIC & CLINICAL PHARMACOLOGY
  • Int'l Joint Research
• [Presentation] Fundamental research for establishment of oral mucositis animal mode (2018)
  • Author(s): Taguchi C, Takeuchi R, Suemitsu M, Morikawa-Saito M, Arikawa K, Kuyama K, Hiratsuka K
  • Organizer: 18th WORLD CONGRESS OF BASIC & CLINICAL PHARMACOLOGY
  • Int'l Joint Research
• [Presentation] Gingival enlargement induced by phenytoin via death receptor signaling pathways (2018)
  • Author(s): Takeuchi R, Matsumoto H, Hiratsuka K
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] 口腔粘膜の炎症性疾患の動物モデル開発 (2018)
  • Author(s): 竹内麗理、田口千恵子、有川量崇、那須郁夫、平塚浩一
  • Organizer: 第67回日本口腔衛生学会・総会
• [Presentation] 口腔粘膜炎モデル動物作製のための基礎的研究 (2018)
  • Author(s): 竹内麗理, 田口千恵子, 末光正昌, 森川美雪, 有川量崇, 松本裕子, 久山佳代, 平塚浩一
  • Organizer: 第38回日本歯科薬物療法学会学術大会
• [Presentation] 口腔内炎症性疾患のラットモデル作製 (2017)
  • Author(s): 竹内麗理, 田口千恵子, 有川量崇, 末光正昌, 森川美雪, 久山佳代, 那須郁夫, 平塚浩一
  • Organizer: 第51回日本実験動物技術者協会総会
• [Presentation] Treatment of gingival overgrowth using 18alpha-glycyrrhetinic acid (2017)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Koichi Hiratsuka
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] 18alpha-glycyrrhetinic acid activates the cytochrome c-medicated death pathway (2017)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Ko Ito, Akinobu Aoki, Kosuke Takahashi, Toshirou Kondoh, Koichi Hiratsuka
  • Organizer: 38th World Congress of the International Union of Physiological Sciences
  • Int'l Joint Research
• [Presentation] Malfunction of death receptor signaling pathways in gingival fibroblasts by phenytoin (2017)
  • Author(s): Reiri Takeuchi, Hiroko Matsumoto, Makiko Ono, Masamichi Komiya, Koichi Hiratsuka
  • Organizer: 第37回日本歯科薬物療法学会学術大会