Department of Social Medicine, Saga Medical School, Saga, 849-8501, Japan.
Department of Chemistry, Fujita Health University School of Health Sciences, Aichi, 470-1192, Japan.
Chem Biol Interact. 2019 Apr 1;302:61-66. doi: 10.1016/j.cbi.2019.01.035. Epub 2019 Feb 2.
Alcohol induces various cutaneous changes, such as palmar erythema and jaundice. However, alcohol-induced skin hyperpigmentation due to melanin deposition has not been reported. Aldehyde dehydrogenase 2 (ALDH2), one of 19 human ALDH isozymes, metabolizes endogenous and exogenous aldehydes to their respective carboxylic acids. Reduced ALDH2 greatly affects acetaldehyde metabolism, leading to its accumulation in the body after the consumption of alcohol and the consequent development of a wide range of phenotypes. In the present study, we report a novel phenotype manifesting in a mouse model with the altered expression of ALDH2. Aldh2 knockout (Aldh2+/- and Aldh2-/-) and wild-type (Aldh2+/+) mice were fed a standard solid rodent chow and a bottle of ethanol solution at concentrations of 0%, 3%, 10%, or 20% (v/v) for more than 10 weeks. The intensity of their skin pigmentation was evaluated by macroscopic observation. Ethanol-exposed Aldh2+/- and Aldh2-/- mice exhibited dose-dependent skin pigmentation in areas of hairless skin, including the soles of the paws and tail; no such changes were observed in wild-type mice. The intensity of skin pigmentation correlated with the number of Aldh2 alleles that were altered in the mice (i.e., 0, 1 and 2 for Aldh2+/+, Aldh2+/-, Aldh2-/-, respectively). Interestingly, the skin pigmentation changes reversed upon the discontinuation of ethanol. The histological examination of the pigmented skin demonstrated the presence of melanin-like deposits, mainly in the epidermis. In conclusion, we report a novel finding that the intake of ethanol induces skin hyperpigmentation in an ALDH2 activity-dependent manner.
酒精可引起各种皮肤变化，如手掌红斑和黄疸。然而，由于黑色素沉积导致的酒精诱导性皮肤色素沉着尚未见报道。醛脱氢酶 2（ALDH2）是 19 种人类 ALDH 同工酶之一，可将内源性和外源性醛代谢为相应的羧酸。ALDH2 活性降低会极大地影响乙醛代谢，导致其在饮酒后在体内积累，并由此产生广泛的表型。在本研究中，我们报告了一种新型表型，该表型在改变 ALDH2 表达的小鼠模型中表现出来。Aldh2 敲除（Aldh2+/- 和 Aldh2-/-）和野生型（Aldh2+/+）小鼠分别喂食标准固体啮齿动物饲料和浓度为 0%、3%、10%或 20%（v/v）的乙醇溶液超过 10 周。通过宏观观察评估其皮肤色素沉着的强度。暴露于乙醇的 Aldh2+/- 和 Aldh2-/- 小鼠在无毛皮肤区域（包括脚掌和尾巴）出现了剂量依赖性的皮肤色素沉着，而野生型小鼠则没有这种变化。皮肤色素沉着的强度与小鼠中改变的 Aldh2 等位基因的数量相关（即 Aldh2+/+、Aldh2+/-、Aldh2-/- 分别为 0、1 和 2）。有趣的是，停止乙醇摄入后皮肤色素沉着发生逆转。对色素沉着皮肤的组织学检查显示存在黑色素样沉积物，主要位于表皮中。总之，我们报告了一个新发现，即乙醇摄入以 ALDH2 活性依赖性方式诱导皮肤色素沉着。
