Résumé
BACKGROUND: Melanin pigmentation plays a major role in normal skin color. The rates of melanin synthesis by melanocytes appear to be regulated by ultraviolet-B(UVB) radiation and chemicals, though the precise mechanisms modulating human epidermal pigmentation are unknown. Several chemicals including arbutin kojic acid(KA), pentadecenoic acid (PDA) and glycolic acid (GA) have been suggested as a meanogenesis inhibitory compounds because of their chemical or biological similarties with hydroquinone or their tyrosinase inhibitory effect. OBJECTIVE: The purpose of this study was to evaluate the inhibitory effect of arbutin, GA, KA and PDA on UV-induced melanogenesis in the vitro and in vivo pigmentary system. METHODS: Cultured normal melanocytes and B-16 melanoma cells, and C57BL mice and human volunteers were used for in vitro and in vivo studies respectively. They were administered to UVB irradiated or nonirradiated cultured normal human melanocytes, and B-16 melanoma cells. For the in vivo study, these chemicals were topically applied to C57BL mice and human volunteer skin after UVB irradiation, Numeric and morphologic changes and melanin content were measured in cultured normal human melanocytes and B-16 melanoma cells. In the C57BL mice, numeric and morphologic changes of split-COPA stained melanocytes were assessed. In the human volunteers, gross pigementary changes were evaluated. RESULTS: 1. The number and melanin content of cultured melanocytes initially decreased after UVB-irradiation, but the melanin content increased 5 days after irradiation. 2. Cell numbers of irradiated or nonirradiated cultured human melanocytes decreased in arbutin(10-3M), KA(10-3M, 10-5M), PDA(10-3M) groups. Those of the cultured B-16 melanoma cells decreased only in the arbutin(10-3M) group after UVB irradiation. 3. Melanin contents of cultured human melanocytes decreased in arbutin(10-3M, 10-5M), KA(10-3M, 10-5M) and PDA(10-3M) groups. Those of cultured B-16 melanoma cells decreased in arbutin(10-3M, 10-5M) groups after UVB-irradiation or nonirradiation. 4. The number of split-DOPA(+) melanocytes decreased in the groups treated with KA 1% for 3, 5 and 7 weeks, KA 0.1%, arbutin 3%, arbutin 5% for 5 and 7 weeks and PDA 5.0% for 7 weeks in the C57BL mice. 5. The number of split-DOPA(+) melanocytes decreased in the groups treated with KA 1.0%, PDA 5.0%, arbutin 3% and arbutin 5% for 5 and 7 weeks and KA 0.1% for 7 weeks in UVB irradiated C57BL mice. 6. Visible inhibition of UVB-induced yperpigmentation was observed in arbutin applied sites in 4 of the 6 volunteers 3 weeks after the application. GA did not show an inhibitory effect on UVB-induced hyperpigmentation in all subjects. CONCLUSION: Arbutn, KA, PDA had a suppressive effect on melanization of nonirradiated melanocytes and melanoma cells as well as UVB-induced hyperpigmentation. It is suggested that these drugs might be candidates as compounds that may control hyperpigmentary disorders.