The fate of melanocytes and the disorganization of basement membrane in a guinea pig model of Rhododendrol-induced chemical vitiligo

Abstract

BackgroundRhododendrol (RD) is a phenolic compound that was first developed as a skin-lightening agent that occasionally induces skin depigmentation. Although it has been shown that RD induces melanocyte death in vitro, it is still not fully understood why melanocytes are gone by RD in vivo. ObjectiveThis research aimed to investigate how melanocytes are eliminated in the animal model by RD. MethodsOn the backs of black guinea pigs (JY-4) with epidermal melanocytes in the basal layer, 30% RD was administered topically three times per day, five days per week. Skin tissues were collected sequentially and histologically analyzed. ResultsOn day 21, L* values in the RD-applied skin were significantly higher than in the vehicle-applied skin. From day 1 to day 7, the number of TRP1-positive melanocytes and melanin in the basal layer decreased, but no TUNEL-positive melanocytes were identified. On the other hand, an accumulation of melanin was newly found in the dermis. Immunohistochemical staining identified several melanocytes in the upper dermis or spinous layer, away from the basement membrane. An investigation of the epidermal-dermal interface showed a structural anomaly in a portion of the basement membrane with elevated MMP2 expression and increased dermal fibroblasts. The application of the MMP2 inhibitor Ilomastat abolished the basement membrane abnormality by RD. ConclusionThese findings suggest that RD-induced alterations in basement membrane structure may contribute to melanocyte detachment and loss, which is the cause of skin depigmentation not only in RD-induced vitiligo but also in vitiligo.