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Web End = Naunyn-Schmiedeberg's Arch Pharmacol (2015) 388:10971104 DOI 10.1007/s00210-015-1144-z
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Effect of thioridazine on antioxidant status of HEMn-DP melanocytes
Micha Otrba1 & Artur Beberok1 & Dorota Wrzeniok1 &
Jakub Rok1 & Ewa Buszman1
Received: 2 February 2015 /Accepted: 5 June 2015 /Published online: 24 June 2015 # The Author(s) 2015. This article is published with open access at Springerlink.com
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 M. 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 M 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 M 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.
Keywords Thioridazine . Melanocytes . Antioxidant enzymes . Hydrogen peroxide
Introduction
Thioridazine is a typical antipsychotic drug belonging to phenothiazine neuroleptics of the piperidine type. It is a mild neuroleptic, displaying sedative and antidepressant effects, which was used in the treatment of positive and negative symptoms of schizophrenia (Wjcikowski et al. 2006). Because of the fact that thioridazine treatment is associated with prolongation of the QT interval, this agent was withdrawn from the market (Buj...