GLUTATHIONE PLAYS A KEY ROLE IN THE DEPIGMENTING AND MELANOCYTOTOXIC ACTION OF N-ACETYL-4-S-CYSTEAMINYLPHENOL IN BLACK AND YELLOW HAIR-FOLLICLES

This study examined the effect of glutathione on the in vivo depigment ing potency of N-acetyl-4-S-cysteaminylphenol (N-acetyl-4-S-CAP) in bl ack and yellow mice after multiple intraperitoneal injections on 10 co nsecutive days. In black mice (C57BL/6J, a/a), N-acetyl-4-S-CAP showed dose-dependent depigmenting potency (0.5, 1.0, and 2.0 mmol/kg), whic h was in parallel to the tissue eumelanin content (98%, 28%, and 3% of controls, respectively) and to the tissue glutathione content (94%, 8 5%, and 76%, respectively). In lethal yellow mice (C57BL/6J, A(y)/a), only a dose of 2.0 mmol/kg showed the color change of hair to dark, no t to white as seen in black mice. This was reflected by the decrease o f pheomelanin content (56%) and the increase of eumelanin content (28% of black mice). The simultaneous administration of N-acetyl-cysteine, which up-regulated glutathione content, completely abolished the depi gmenting potency of N-acetyl-4-S-CAP, whereas administration of buthio nine sulfoximine, which depleted the tissue glutathione content, enhan ced the depigmenting potency of N-acetyl-4-S-CAP in black hair. In yel low mice, the darkening of hair follicles by 2.0 mmol/kg of N-acetyl-4 -S-CAP was completely abolished by the combined administration of N-ac etyl-cysteine, with the resulting hair color the same as in controls, whereas combined administration with buthionine sulfoximine caused som e whitening of yellow hair follicles. Our data indicate that the tissu e content of glutathione regulates melanocytotoxicity and depigmenting potency of N-acetyl-4-S-CAP and that this alteration of glutathione c ontent may switch the melanogenesis type from pheomelanin to eumelanin .