Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Department of Chemistry, Fujita Health University School of Health Sciences, Toyake, Aichi, Japan.
Exp Dermatol. 2018 Jul;27(7):754-762. doi: 10.1111/exd.13555.
4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity-dependent manner. 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 epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N-acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress-induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl-RD-catechol and RD-pheomelanin in NHEMs 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 help to elucidate the development mechanisms of RD-induced leukoderma and provide information for innovation of safe skin-whitening compounds.
4-(4-羟苯基)-2-丁醇（杜鹃醇，RD）是一种皮肤美白剂，据报道，它会导致一些使用者的皮肤脱色，这归因于它对黑素细胞的细胞毒性。据报道，这种对黑素细胞的细胞毒性可能是通过依赖于酪氨酸酶活性的氧化应激来介导的。我们研究了紫外线辐射（UVR）对 RD 诱导的黑素细胞毒性的影响，因为它是一个额外的加重因素。UVR 通过诱导内质网（ER）应激，增强了正常人类表皮黑素细胞（NHEMs）中 RD 诱导的细胞毒性。检测到细胞内活性氧（ROS）的生成增加。用 N-乙酰半胱氨酸（NAC）预处理，抗氧化剂和谷胱甘肽的前体，可显著减轻 RD 和 UVR 处理的 NHEMs 中的 ER 应激诱导的细胞毒性。在 RD 和 UVR 处理的 NHEMs 中，半胱氨酰-RD-儿茶酚和 RD-真黑素的增加表明，在 UVR 激发后，RD 或 RD 代谢物是有效的 ROS 生成物质，并且在黑色素生成过程中产生 RD-真黑素的趋势会放大黑素细胞中的 ROS 生成。我们的结果有助于阐明 RD 诱导的白癜风的发展机制，并为安全美白化合物的创新提供信息。
