title: Depigmentation caused by application of the active brightening material, rhododendrol, is related to tyrosinase activity at a certain threshold.
abstract: BACKGROUND
  Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol.
  
  
  OBJECTIVE
  To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed.
  
  
  METHODS
  The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase.
  
  
  RESULTS
  Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity.
  
  
  CONCLUSIONS
  The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishment of the melanocyte viability by rhododendrol.
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasamatsu
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan. Electronic address: hachiya.akira@kao.co.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Hachiya
authors.affiliation: Analytical Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Analytical Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Fujimori
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takano
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Moriwaki
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hase
authors.affiliation: Department of Dermatology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Dermatology, Fujita Health University School of Medicine, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsunaga
mesh_terms: D057886:Bleaching Agents / Q000737:chemistry*; D000440:Butanols / Q000737:chemistry*; D002470:Cell Survival; D006801:Humans; D017496:Hypopigmentation / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects
chemical_list: D057886:Bleaching Agents; D000440:Butanols; D008543:Melanins; D034741:RNA, Small Interfering; C115945:rhododendrol; D014442:Monophenol Monooxygenase
keywords: Depigmentation; Hydroxyl-rhododendrol; Melanocyte; Rhododendrol; Tyrosinase; White blotching