Dual role of melanins and melanin precursors as photoprotective and phototoxic agents: inhibition of ultraviolet radiation-induced lipid peroxidation.
Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective mechanism of mammalian skin against radiation damage. The melanin pigments, eumelanin and pheomelanin, are likely to be important in protection against UVR, but their precursors are generally considered as phototoxic. The available data suggest DNA damage as the mechanism of phototoxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more relevant (from the point-of-view of the melanosomal confinement of these molecules) mechanism of phototoxicity, not known. As a model system for UVR-melanin-membrane interactions, we irradiated liposomes in the presence of eumelanin, pheomelanin and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD). The presence of the two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure. The antioxidant activity of the melanin precursors was diminished under strong prooxidant conditions (presence of Fe3+). These results suggest that melanin precursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.
Schmitz
S
S
Department of Physiology, University of Alberta, Edmonton, Canada.
Thomas
P D
PD
Allen
T M
TM
Poznansky
M J
MJ
Jimbow
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003548:Cysteinyldopa / Q000494:pharmacology*; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000528:radiation effects*; D008081:Liposomes / Q000378:metabolism / Q000528:radiation effects; D008543:Melanins / Q000494:pharmacology / Q000502:physiology*; D008974:Mollusca; D010713:Phosphatidylcholines / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000975:Antioxidants; D007211:Indoles; D008081:Liposomes; D008543:Melanins; D010713:Phosphatidylcholines; D011837:Radiation-Protective Agents; C018362:pheomelanin; C041877:eumelanin; D003548:Cysteinyldopa; C033871:5,6-dihydroxyindole