Rhododenol-induced leukoderma in a mouse model mimicking Japanese skin
Rhododenol-induced leukoderma in a mouse model mimicking Japanese skin
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DOI：
10.1016/j.jdermsci.2015.10.011
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发表时间：
2016-01-01
影响因子：
4.6
通讯作者：
Suzuki, Tamio
中科院分区：
文献类型：
--
作者：
Abe, Yuko;Okamura, Ken;Suzuki, Tamio
背景：Rhododenol， 4-（4-羟基苯基）-2-丁醇，Rhododenol (R) （RD）是一种天然存在的酚类化合物，作为酪氨酸酶抑制剂被开发用于美白化妆品。2013年，使用含有rd的美白化妆品的消费者出现了皮肤色素沉着；这种情况被称为rd诱导的白皮病。目的：rd诱导白皮病的病因尚不清楚。为了评估RD的脱色潜力，我们通过局部应用RD建立了一种新的白皮病小鼠模型。方法：以表皮分布有黑素细胞的无毛hk14-SCF Tg小鼠为研究对象。每日将RD涂抹于小鼠背部皮肤，连续28 d。然后，对这些小鼠的活检样本进行免疫组织学、生化和电镜分析。结果：rd处理部位在第14天出现色素沉着。组织学检查显示第7天表皮黑色素细胞丢失。另一方面，与无毛的hk14-SCF Tg具有相同背景的白化小鼠的黑素细胞数量没有减少，但没有酪氨酸酶活性。生化分析表明，rd处理部位的真黑素含量下降，rd醌的代谢产物，即非蛋白硫醇加合物和蛋白sh加合物产生。电镜分析显示含有电子致密物质的双膜壁结构，这可能是典型的含黑色素的自噬体和内质网（ER）的扩张，这可能表明内质网应激。结论：这些数据表明，RD发挥酪氨酸酶依赖性黑素细胞的细胞毒性，而自噬途径激活引起的酪氨酸酶依赖性内质网应激积累有助于黑素细胞的细胞毒性。(C) 2015日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol (R) (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced leukoderma.Objective: The etiology of RD-induced leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of leukoderma by topically applying RD.Methods: Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice.Results: The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD-treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double-membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress.Conclusions: These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase-dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.