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Role of oxidative stress in the cytotoxicity caused by skin whitening agents

Research Project

Project/Area Number 16K10156
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKobe University

Principal Investigator

Nishigori Chikako  神戸大学, 医学研究科, 教授 (50198454)

Co-Investigator(Kenkyū-buntansha) 永井 宏  神戸大学, 医学研究科, 准教授 (80335447)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsメラノサイト / 紫外線 / 美白剤 / ERストレス / 白斑 / N-アセチルシステイン / 酸化ストレス / アポトーシス / 色素細胞 / グルタチオン / ロドデノール / UVB / 小胞体ストレス / 活性酸素 / 表皮角化細胞
Outline of Final Research Achievements

Pathemechanisms of chemicalleukoderma was investigated using a skin whitening agent, 4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD). We examined the effect of UV radiation (UVR) on RD-induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD-induced cytotoxicity in normal human melanocytes via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pre-treatment with N-acetyl cysteine significantly attenuated ER stress-induced cytotoxicity in melanocytes treated with RD and UVR. Increase in cysteinyl-RD-catechol and RD-pheomelanin in melanovytes treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS-generating substances and that the tendency to produce RD-pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results imply a possible usefulness of N-acetyl cytsteine as a treatment drug for leukoderma.

Academic Significance and Societal Importance of the Research Achievements

美白剤を含む化学物により白斑が引き起こされることがあり、化学白斑とか職業性白斑と呼ばれるが、その化学物質に曝露された全員が発症するわけではなく、一旦引き起こされると治療が難しい例もある。今回の結果から、化学物質単独では色素細胞の障害を起こさないような常用量であっても、紫外線炎症をはじめとする炎症が惹起されている条件下であれば、酸化ストレス誘導により白斑が引き起こされやすくなる可能能性があること、また、そのような炎症を抑える薬物は白斑の治療薬と成り得ることを示唆しており、一般の日用品のユーザーにも有益な情報となる。

Report

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

    (3 results)

All 2018 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) Book (1 results)

  • [Journal Article] 4-(4-Hydroxyphenyl)-2-butanol (rhododendrol)-induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress2018

    • Author(s)
      Goto Noriko、Tsujimoto Mariko、Nagai Hiroshi、Masaki Taro、Ito Shosuke、Wakamatsu Kazumasa、Nishigori Chikako
    • Journal Title

      Experimental Dermatology

      Volume: Epub Issue: 7 Pages: 754-762

    • DOI

      10.1111/exd.13555

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] N-acetylcysteine (NAC)は紫外線によるロドデノールの色素細胞障害性増強効果を軽減する2016

    • Author(s)
      後藤典子, 辻本昌理子, 永井宏, 正木太朗, 伊藤祥輔, 若松一雅, 錦織千佳子
    • Organizer
      第27回日本色素細胞学会年次学術大会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜県岐阜市)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Book] 最新美容皮膚科診療ナビゲーション2018

    • Author(s)
      錦織千佳子
    • Total Pages
      184
    • Publisher
      学研メディカル秀潤社
    • ISBN
      9784780909524
    • Related Report
      2018 Annual Research Report

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

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