Effects of 4-tertiary butyl catechol on glutathione-metabolizing enzymes in vivo and in vitro.
4-Tertiary butyl catechol (TBC) causes depigmentation in humans and animals and stimulates formation of pheomelanosomes. In this study, we investigated the effects of noncytotoxic doses of TBC on glutathione S-transferase (GST) activity in the skin of Uscd strain mice and B16 murine melanoma cells in culture, in relation to changes in activities of glutathione reductase (GR) and gamma-glutamyl transpeptidase (GGT) reported to be involved in pheomelanogenesis. Occurrence of pheomelanosomes in skin melanocytes was demonstrated by electron microscopy and reduction (25%) of eumelanin content in melanoma cells was shown by spectrophotometry. Topical application of 1 M TBC-DMSO-acetone solution on the ear skin elevated GST activity about 27%, and activities of GGT and GR to 35% and 19%, respectively, within 1 week. Melanoma cells cultured in 10(-4) M TBC-containing medium for 2 h showed no changes in GST and GGT activities, but 12% increase of GR activity during the first 12 h. Activities of all 3 enzymes was elevated (11-17%) 24 h later. The elevation detected by 48 h was 25% for GST, 26% for GGT, and 14% for GR. The findings were interpreted to show that depigmentation produced by the antioxidant results from stimulated pheomelanogenesis through activation of glutathione-metabolizing enzymes and suppressed oxidation of eumelanin intermediates.
D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002460:Cell Line; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000648:ultrastructure; D008545:Melanoma / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D012867:Skin / Q000201:enzymology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002396:Catechols; D008543:Melanins; C015047:p-tert-butyl catechol; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase