Zebrafish as a new model for rhododendrol‐induced leukoderma

Abstract

Rhododendrol (RD: 4-(4-Hydroxyphenyl)-2-butanol) is a melanogenesis inhibitor isolated from the stem bark of Acer nikoense MAXIM.Since RD is structurally similar to L-tyrosine, it competitively inhibits tyrosinase, a rate-limiting enzyme for melanin synthesis (Akazawa et al., 2006). RD was approved as an ingredient in cosmetics for skin lightening in Japan in 2008; however, 5 years later, cosmetic products containing RD were recalled because of the development of depigmentation (idiopathic leukoderma or vitiligo) in the skin. The total number of patients with leukoderma caused by RD was 19,605, accounting for 2%-2.5% of users of the RD-included cosmetic products (Nishigori et al., 2015). Although the symptoms of RD-induced leukoderma were improved or eliminated in 72% of patients, the remaining patients were resistant to conventional therapy (Watabe et al., 2018).A study with cultured melanocytes has reported that tyrosinase converts RD to cytotoxic metabolites, such as RD-catechol and RD-cyclic catechol, which cause melanocyte-specific cell death