title: Melanogenesis and antioxidant defense system in normal human  melanocytes cultured in the presence of chlorpromazine.
abstract: Chlorpromazine is used in the treatment of schizophrenia and psychotic disorders and belongs to phenothiazine class of neuroleptic drugs. It shows severe side effects such as extrapyramidal symptoms as well as ocular and skin disorders, but the mechanism is still not fully established. The aim of this study was to examine the effect of chlorpromazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been demonstrated that chlorpromazine induces concentration dependent loss in cell viability. The value of EC(50) was calculated to be 2.53 μM. Chlorpromazine in lower concentrations (0.0001, 0.001 and 0.01 μM) increased the melanin and microphthalmia-associated transcription factor (MITF) content and tyrosinase activity, while changes of antioxidant enzymes activity were not observed. It suggests that long-term chlorpromazine therapy, even with low drug doses, may lead to hyperpigmentation disorders in skin and/or eye. The use of the analyzed drug in higher concentrations (0.1 and 1.0 μM) caused significant alterations of antioxidant enzymes activity in normal melanocytes, what may explain a potential role of chlorpromazine in the depletion of cellular antioxidant status leading to other adverse effects associated with the high-dose and/or long-term therapy.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, PL 41-200 Sosnowiec, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Otreba
authors.forename: Dorota
authors.initials: D
authors.lastname: Wrześniok
authors.forename: Artur
authors.initials: A
authors.lastname: Beberok
authors.forename: Jakub
authors.initials: J
authors.lastname: Rok
authors.forename: Ewa
authors.initials: E
authors.lastname: Buszman
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis*; D008544:Melanocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014442:Monophenol Monooxygenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D008543:Melanins; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D014442:Monophenol Monooxygenase; D013482:Superoxide Dismutase; D002746:Chlorpromazine