title: Effect of thioridazine on antioxidant status of HEMn-DP melanocytes.
abstract: Thioridazine as an antipsychotic agent was extensively used to treat various psychotic disorders, e.g. schizophrenia. However, the therapy with this drug can induce serious side effects such as extrapyramidal symptoms or ocular and skin disorders, which mechanisms are still not fully established. To gain inside the molecular mechanisms underlying thioridazine toxicity, we examined the effect of this drug on cell viability, antioxidant defence system as well as melanogenesis in normal human melanocytes. It was demonstrated that thioridazine induces concentration-dependent loss in cell viability. The value of EC50 was calculated to be 2.24 μM. To study the effect of thioridazine on antioxidant defence system in melanocytes, the level of hydrogen peroxide and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were determined. The drug in concentrations of 0.1, 0.25, 1.0 and 2.5 μM caused changes in cellular antioxidant defence system indicating the induction of oxidative stress. It was also shown that the analysed neuroleptic in concentrations of 1.0 and 2.5 μM significantly inhibited melanogenesis. The observed changes in cell viability, antioxidant defence system and melanization in normal human melanocytes after thioridazine treatment may explain an important role of reactive oxygen species as well as melanin in mechanisms involved in this drug side effects directed on pigmented tissues.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, PL 41-200, Sosnowiec, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Otręba
authors.forename: Artur
authors.initials: A
authors.lastname: Beberok
authors.forename: Dorota
authors.initials: D
authors.lastname: Wrześniok
authors.forename: Jakub
authors.initials: J
authors.lastname: Rok
authors.forename: Ewa
authors.initials: E
authors.lastname: Buszman
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013881:Thioridazine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D008543:Melanins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D013881:Thioridazine