817 Ethanol induces skin hyperpigmentation in mice with aldehyde dehydrogenase 2 deficiency

      Excessive alcohol consumption leads to alcohol use disorder. Alcohol is metabolized to acetaldehyde, which is then oxidized to acetic acid by aldehyde dehydrogenases (ALDH), a class of enzymes that facilitate the conversion of aldehydes to their corresponding acids. Among ALDHs, mitochondrial ALDH2 is the primary enzyme involved in the metabolism of acetaldehyde. In addition to its well-known role in ethanol metabolism, recent studies have suggested that ALDH2 dysfunction is associated with a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, cancer, anemia, pain, osteoporosis and aging. However, the role of ALDH2 has not been well investigated in the skin. In this study, we studied the effect of the functional defect of Aldh2 using Aldh2 KO mice. Ten-week-old Aldh2 KO mice and control C57BL/6 (WT) mice were fed with a standard hard diet and bottled water with ethanol for 10 weeks. A dose-dependent skin pigmentation was observed in the ears, feet, tail and genital area in Aldh2 KO mice but not WT mice (p = 0.08–0.95; p interaction <0.001). The pigmentation was mainly localized in the epidermis and partially in the dermis, and found to be melanin. Analysis of degradation products of melanin demonstrated ethanol dose-dependent production of eumelanin in the mouse skin. Immunohistochemical analysis showed ethanol-induced melanocyte proliferation in Aldh2 KO mice. Acetaldehyde exposure occurs not only by ethanol consumption but also by a volatile organic compound, smoking and food products. ALDH2 enzyme is inactivated by post-translational modification under increased oxidative/nitrosative stress, suggesting the role of ALDH2 in acetaldehyde-induced skin even in individuals without a defective polymorphism of ALDH2.