Substantial evidence for the rhododendrol-induced generation of hydroxyl radicals that causes melanocyte cytotoxicity and induces chemical leukoderma. Issue 3 (September 2018)

• Record Type: Journal Article
• Authors: Gabe, Yu; Miyaji, Akimitsu; Kohno, Masahiro; Hachiya, Akira; Moriwaki, Shigeru; Baba, Toshihide
• Is Part Of: Journal of dermatological science. Volume 91:Issue 3(2018)
• Page Start: 311
• Page End: 316
• Publication Date: 2018-09
• Subjects: Hydroxyl radical -- Leukoderma -- Antioxidant response -- Rhododendrol -- Glutathione; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2018.06.007
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Elaborate hydroxyl radical detection after rhododendrol application to melanocytes. Remarkable correlation of hydroxyl radical generation with melanocyte cytotoxicity. Suppressing both hydroxyl radicals and cytotoxicity by enhancing glutathione levels. Useful strategy to prevent leukoderma induced by phenol derivatives. Abstract: Background: Rhododendrol (4-(4-hydroxyphenyl)-2-butanol) has been used as a lightening/whitening cosmetic but was recently reported to induce leukoderma. Although rhododendrol has been shown to be transformed by tyrosinase to hydroxyl-rhododendrol, which is cytotoxic to melanocytes, its detailed mechanism of action including the involvement of reactive oxygen species is not clearly understood. Objective: To confirm the relationship of hydroxyl radical generation to melanocyte cytotoxicity induced by rhododendrol, this study was performed. Methods: An electron spin resonance method with a highly sensitive detection system was utilized to monitor hydroxyl radicals generated from two distinct normal human epidermal melanocyte lines with different levels of tyrosinase activity after the addition of various amounts of rhododendrol. Cytotoxicity of rhododendrol was analyzed by AlamarBlue assay under the same condition. Results: Hydroxyl radicals were generated depending on the amounts of rhododendrol and/or tyrosinase. After the correlation between hydroxyl radical generation with melanocyte viability was confirmed, an inhibitor of oxidative stress, N -acetyl cysteine, was shown to dramatically diminish rhododendrol-induced generation of hydroxyl radicals and melanocyte cytotoxicity by increasing glutathione levels. In contrast, buthionine sulfoximine, which depletes glutathione, augmented both of those parameters. Conclusion: Suppressing oxidative stress would prevent and/or mitigate some phenol derivative-induced leukoderma by avoiding hydroxyl radical-initiated melanocyte cytotoxicity.