Properties of melanin pigments for the definition of mechanisms of (photo)toxicity in red hair phenotype and development of strategies of (photo)protection.

Abstract

In recent years particular attention has been focused on the properties of melanin pigments with regard to their association with some pathological conditions and to their controversial role in the response of skin to solar radiation. This is especially true in the case of pheomelanins, typical of red hair phenotype, with red hair pale skin, blue-green eyes and freckles. People exhibiting this phenotype have poor tanning capacity, exhibit a UV-susceptibility trait with high tendency to sunburn and an increased risk for skin tumors and melanoma. On the other hand, eumelanins are commonly believed to be the most important photoprotective factor, even if evidence accumulating over the last decades highlight a much more controversial role of eumelanins in human pigmentation. On these bases, the research work carried out during the PhD course and reported in this thesis was directed at investigating the light-independent effects of purified human hair melanins on keratinocyte cell cultures with particular attention to their pro-oxidant properties and at defining the origin of the broadband absorption spectrum of eumelanin, which underpins their protective shielding effect. Based on the consideration that, besides eumelanin pigments, the entire melanogenic pathway is relevant to melanocyte function, the effect of carboxyl group substituent of indole precursors on eumelanin properties was evaluated and a suitable derivative of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) was prepared to assess the photoprotective properties for potential application in sunscreen formulations. Local excess of pigmentation is one of the most common pigmentary disorder5 whose aesthetically impact has urged the search for efficient strategies for control of skin pigmentation. As a preliminary approach toward the implementation of a novel skin depigmenting agent a conjugate of caffeic acid with dihydrolipoic acid was prepared and tested for its ability to inhibit mushroom tyrosinase activity.