title: Peroxidase-mediated mechanisms are involved in the melanocytotoxic and melanogenesis-inhibiting effects of chemical agents.
abstract: Melanogenesis is based on the enzymatic conversion of the amino acid tyrosine, through a series of intermediates, to melanin pigments. The nature of the enzymes involved in the different steps of melanogenesis has been intensely debated. However, it is now believed that tyrosinase is responsible for the conversion of tyrosine to dopa and of dopa to dopaquinone, and that peroxidase accomplishes the oxidative polymerization of the eventually formed indoles to eumelanin pigments. Some very few investigators have also considered a main role for peroxidase in initiating melanogenesis. At present, most different hypotheses are focused on tyrosinase-mediated mechanisms to elucidate the melanocytotoxic and depigmenting activities of chemicals. However, many properties of these agents cannot be explained by such mechanisms. Most of the melanocytotoxic agents (e.g. hydroquinone, catechols, butylated hydroxyanisole) can be converted to cytotoxic species, such as quinones, by the peroxidase-H(2)O(2) system. On the other hand, many of the melanogenesis inhibitors which are not known to inhibit tyrosinase (e.g. glucocorticoids, ascorbic acid, indomethacin) have the capacity to strongly inhibit peroxidase activity. We have proposed that peroxidase-mediated mechanisms, in addition to or in several instances rather than tyrosinase-mediated mechanisms, can explain the melanocytotoxic and depigmenting properties of such agents.
authors.forename: Behrooz
authors.initials: B
authors.lastname: Kasraee
mesh_terms: D000818:Animals; D002396:Catechols / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology / Q000633:toxicity; D017495:Hyperpigmentation / Q000188:drug therapy; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology*; D008550:Melatonin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008713:Methimazole / Q000494:pharmacology / Q000633:toxicity; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D002396:Catechols; D006873:Hydroquinones; D008543:Melanins; D008713:Methimazole; D009195:Peroxidase; D014442:Monophenol Monooxygenase; D008550:Melatonin; C031927:hydroquinone