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A basic study for health effects of cationic surfactants

Research Project

Project/Area Number 18H03043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionNational Institute for Environmental Studies

Principal Investigator

Seishiro Hirano  国立研究開発法人国立環境研究所, 環境リスク・健康領域, フェロー (20150162)

Co-Investigator(Kenkyū-buntansha) 菅野 さな枝  名古屋市立大学, 医薬学総合研究院(医学), 講師 (50391090)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords陽イオン / 粒子状物質 / 表面活性 / 肺 / マクロファージ / 毒性発現機構 / 細胞 / 生体影響 / 細胞毒性 / 炎症
Outline of Final Research Achievements

Benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC) are potential pulmonary toxicants, when inhaled as aerosols. The surface pressure/trough area (π-A) isotherm feature and atomic force microscopy (AFM) images of lipid monolayers indicated that BAC and CPC change physiological functions of the alveolar lining. Exposure to BAC and CPC caused caspase 3-dependent apoptotic cell death in A549 cells and the cytotoxicity increased with the length of the alkyl chain of BAC. Our study indicates that aerosolized BAC and CPC can be internalized into alveolar cells via Macrophage Receptor with Collagenous Structure (MARCO) which recognizes the surface of unopsonized environmental particles. We have also shown that BAC and CPC activate the inflammasome in macrophages and induce stress granules in G3BP1-expressing cell. Together, the current study shows mechanistic pathways, whereby cationic detergents cause severe inflammation in the lung when inhaled as aerosols.

Academic Significance and Societal Importance of the Research Achievements

抗菌作用があるため消毒用の日用品として広く使われている塩化ベンザルコニウムや塩化セチルピリジニウムなどの陽イオン界面活性剤は、ミストとして吸入した場合、肺の炎症と呼吸不全を起こすことが知られている。本研究では、これらの陽イオン界面活性剤が肺胞を被覆しているサーファクタントに及ぼす影響を、物理化学的手法を用いることによりはじめて定量的に示した。また、陽イオン界面活性剤の細胞毒性をはじめ、炎症作用にアポトーシスやインフラマゾームが関与していることを明らかにした。これらの生体作用機序に関する研究成果は、陽イオン界面活性剤の安全使用に関する重要な指針を与えるものと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (9 results)

All 2022 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Scavenger receptor MARCO contributes to cellular internalization of exosomes by dynamin-dependent endocytosis and micropinocytosis.2020

    • Author(s)
      Sanae Kanno, Seishiro Hirano, Tsubasa Sakamoto, Akiko Furuyama, Hiroshi Takase, Hideaki Kato, Mamiko Fukuta, Yasuhiro Aoki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21795-21795

    • DOI

      10.1038/s41598-020-78464-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Benzalkonium chloride and cetylpyridinium chloride induce apoptosis in human lung epithelial cells and alter surface activity of pulmonary surfactant monolayers2020

    • Author(s)
      Kanno Sanae、Hirano Seishiro、Kato Hideaki、Fukuta Mamiko、Mukai Toshiji、Aoki Yasuhiro
    • Journal Title

      Chemico-Biological Interactions

      Volume: 317 Pages: 108962-108962

    • DOI

      10.1016/j.cbi.2020.108962

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relevance of autophagy markers to cytotoxicity of zinc compounds in macrophages2020

    • Author(s)
      Hirano Seishiro、Kanno Sanae
    • Journal Title

      Toxicology in Vitro

      Volume: 65 Pages: 104816-104816

    • DOI

      10.1016/j.tiv.2020.104816

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization and influence of hydroxyapatite nanopowders on living cells2018

    • Author(s)
      Oberbek Przemyslaw、Bolek Tomasz、Chlanda Adrian、Hirano Seishiro、Kusnieruk Sylwia、Rogowska-Tylman Julia、Nechyporenko Ganna、Zinchenko Viktor、Swieszkowski Wojciech、Puzyn Tomasz
    • Journal Title

      Beilstein Journal of Nanotechnology

      Volume: 9 Pages: 3079-3094

    • DOI

      10.3762/bjnano.9.286

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 陽イオン性殺菌剤曝露によるヒト肺胞上皮細胞への細胞膜毒性2021

    • Author(s)
      菅野さな枝、平野靖史郎、大瀧純、加藤秀章、福田真未子、中村昌美、青木康博
    • Organizer
      第40年会日本法中毒学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Effects of developmental exposure to secondary organic aerosols on immune cells and apoptosis in rat brain.2021

    • Author(s)
      Tin-Tin-Win-Shwe, Chaw Kyi Tha Thu, Fujitani Y.,Shinji Tsukahara, and Seishiro Hirano
    • Organizer
      日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cytotoxicity of cationic disinfectants through apoptosis in human alveolar epithelial cells.2019

    • Author(s)
      Sanae Kanno, Seishiro Hirano, Jun Otaki, Hideaki Kato, Mamiko Fukuta, Yoshimi Nakamura, Tetsuya Horita, Yasuhiro Aok
    • Organizer
      The 57th Annual Meeting of the International Association of Forensic Toxicologist (TIAFT)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト肺胞上皮細胞を用いた陽イオン性殺菌剤曝露による細胞毒性とアポトーシス誘導2019

    • Author(s)
      菅野 さな枝、平野靖史郎、大瀧 純、加藤 秀章、福田 真未子、堀田 哲也、中村 昌美、青木 康博
    • Organizer
      第38年会 日本法中毒学会
    • Related Report
      2019 Annual Research Report
  • [Book] Autophagy as a Biomarker of Cytotoxicity. In: Patel V.B., Preedy V.R., Rajendram R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications.2022

    • Author(s)
      Seishiro Hirano
    • Total Pages
      20
    • Publisher
      Springer Cham.
    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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