4-(4-Hydroxyphenyl)-2-butanol (rhododendrol)-induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress
4-(4-Hydroxyphenyl)-2-butanol (rhododendrol)-induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress
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DOI：
10.1111/exd.13555
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发表时间：
2018-07-01
影响因子：
3.6
通讯作者：
Nishigori, Chikako
中科院分区：
文献类型：
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作者：
Goto, Noriko;Tsujimoto, Mariko;Nishigori, Chikako
据报道，4-(4-羟基苯基)-2-丁醇（杜鹃醇，RD）是一种皮肤美白剂，据报道会导致一些使用者皮肤色素脱失，这是由于其对黑素细胞的细胞毒性。据报道，对黑素细胞的细胞毒性可能是由氧化应激以酪氨酸酶活性依赖性方式介导的。我们检查了紫外线辐射 (UVR) 对 RD 诱导的黑素细胞细胞毒性的影响，作为一个额外的加重因素。 UVR 通过诱导内质网 (ER) 应激增强 RD 诱导的正常人表皮黑素细胞 (NHEM) 细胞毒性。检测到细胞内活性氧（ROS）的产生增加。在用 RD 和 UVR 处理的 NHEM 中，用 N-乙酰半胱氨酸 (NAC)、抗氧化剂和谷胱甘肽前体进行预处理可显着减弱 ER 应激诱导的细胞毒性。经RD和UVR处理的NHEM中半胱氨酰-RD-儿茶酚和RD-褐黑素的增加表明，在UVR激发后，RD或RD代谢物是有效的ROS生成物质，并且在黑素生成过程中产生RD-褐黑素的趋势放大了黑素细胞中ROS的生成。我们的研究结果有助于阐明 RD 诱导的白斑病的发生机制，并为安全美白化合物的创新提供信息。
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.