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The in vivo melanocytotoxicity and depigmenting potency of N‐2,4‐acetoxyphenyl thioethyl acetamide in the skin and hair
Author(s) -
JIMBOW M.,
MARUSYK H.,
JIMBOW K.
Publication year - 1995
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.1995.tb02699.x
Subject(s) - depigmentation , melanosome , in vivo , chemistry , melanin , potency , tyrosinase , black hair , human skin , pharmacology , ex vivo , in vitro , biochemistry , dermatology , biology , medicine , enzyme , genetics , microbiology and biotechnology
Summary It has been shown previously that N‐acetyl‐4‐S‐cysteaminylphenol (N‐Ac‐4‐S‐CAP) is a tyrosinase Substrate and a potent depigmenting agent of dark skin and black hair. The present study evaluated the depigmenting potency of an acetyl derivative of N‐Ac‐4‐S‐CAP. N‐2,4‐acetoxyphenyl thioethyl acetamide (NAP‐TKA) in the skin and hair. We tested for (i) in vitro metabolites in the skin after topical application. and (ii) in vivo depigmenting potency in the skin and hair. We found that NAPTEA was stable in water. but was converted to N‐Ac‐4‐S‐CAP after topical application to human skin. Therefore. although NAP‐TEA was not a tyrosinase substrate. it could react with tyrosinase after being converted to N‐Ac‐4‐S‐CAP by 0‐deacetylation in vivo. NAP‐TEA produced marked depigmentation of dark skin (Yucatan pig) after daily topical application. When given by intraper‐itoneal injection. it resulted in complete loss of hair colour (white) grown at the epilated site in adnlt C57 black mice after daily administration for l0 days, and incomplete loss of coat colour (silver grey) in newborn C57 black mice after a single administration, The depigmentation of the skin and hair was reversible, Splil‐dopa preparalion and eieclron microsnipy indicated thal lliis depigmentation is primarily related to (i) a marked decrease in the number of functioning melanocytes and melanized melanosomes, (ii) a decrease in the number of melanosomes transferred to keratinocytes, and (iii) selective degeneration/inactivation of melanocytes. and deposition of melanin‐like malerial in the Golgi cisternae. coated vesicles and melanosomes. where tyrosinase is reported to be located. We propose the NAP‐TEA is converted in vivo to N‐Ac‐4‐.S‐CAP which. via interaction with tyrosinase. causes reversible depigmentation of the skin and hair.