Enhancement of the depigmenting effect of hydroquinone by cystamine and buthionine sulfoximine.
Glutathione (GSH) performs several important biological functions, including quenching of reactive oxygen species, and protection of cells from toxic compounds such as quinones. The first step in the synthesis of GSH is catalysed by gamma-glutamylcysteine synthetase, an enzyme which is inhibited by cystamine and buthionine sulfoximine (BSO). In this study, we examined the possibility that the effect of hydroquinone (HQ) on pigmentation could be potentiated by inhibiting the production of GSH. In vitro studies using melanoma cell lines demonstrated that both cystamine and BSO could potentiate the inhibitory effects of HQ on tyrosinase activity and melanin content. A synergistic decrease in hair pigmentation was observed when a combination of HQ (2 or 4%) and BSO (5%) was applied to the dorsal skin of C57BL mice. In black hairless guinea-pigs, the application of HQ plus either BSO or cystamine resulted in a significant decrease in epidermal pigmentation when compared with any of the agents alone. The possibility exists that in the future a combination of HQ plus cystamine or BSO could be used to treat disorders such as melasma and post-inflammatory hyperpigmentation.
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510, USA.
J L
JL
Bolognia
S A
SA
Sodi
M P
MP
Osber
J M
JM
Pawelek
D000818:Animals; D019328:Buthionine Sulfoximine; D003538:Cystamine / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006200:Hair Color / Q000187:drug effects*; D006873:Hydroquinones / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D012880:Skin Pigmentation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D014442:Monophenol Monooxygenase; D003538:Cystamine; C031927:hydroquinone