1209 The fate of melanocytes and the disorganization of basement membrane in a guinea pig model of rhododendrol-induced chemical vitiligo

Rhododendrol (RD) is a phenolic compound that was first developed as a skin-lightening agent that occasionally induces skin leukoderma. 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. This research aimed to investigate how melanocytes are eliminated in the animal model by RD. On 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. On day 21, L* values (brightness index) in the RD-applied area were significantly higher than in the vehicle control area. On day 14, RD has already induced obvious skin depigmentation in several animals. 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 using electron microscopy showed a structural anomaly in a portion of the basement membrane. This shows that the aberrant basement membrane structure induced by RD might be responsible for the melanocyte detachment and decrease of melanocytes, which is the cause of skin depigmentation. This in vivo model gives a different perspective from the in vitrofindings and may be used to elucidate a novel mechanism of action not only for RD-induced leukoderma but also for vitiligo, and the fate of lesional melanocytes should be further investigated.