The Effects of Cimetidine, N-Acetylcysteine, and Taurine on Thioridazine Metabolic Activation and Induction of Oxidative Stress in Isolated Rat Hepatocytes

Thioridazine (TZ) is used commonly in the treatment of schizophrenia. However, its clinical use has been associated with liver toxicity. Therefore, we examined the cytotoxic effect of TZ on freshly isolated rat hepatocytes to evaluate the role of TZ pathogenesis in hepatotoxicity. In addition, the e...

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Bibliographic Details
Published in:Pharmaceutical chemistry journal 2018-02, Vol.51 (11), p.965-969
Main Authors: Eftekhari, Aziz, Ahmadian, Elham, Azarmi, Yadollah, Parvizpur, Alireza, Fard, Javad Khalili, Eghbal, Mohammad Ali
Format: Article
Language:English
Subjects:
Acetylcysteine
Cell death
Cimetidine
Lipid peroxidation
Medicine
Organic Chemistry
Pharmacology/Toxicology
Pharmacy
Phenothiazines
Schizophrenia
Taurine
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Summary:Thioridazine (TZ) is used commonly in the treatment of schizophrenia. However, its clinical use has been associated with liver toxicity. Therefore, we examined the cytotoxic effect of TZ on freshly isolated rat hepatocytes to evaluate the role of TZ pathogenesis in hepatotoxicity. In addition, the effect of N-acetylcysteine (NAC), taurine, and cimetidine on this toxicity was investigated. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), cellular glutathione (GSH) content, and mitochondrial depolarization were assessed as toxicity markers. Results showed that TZ caused an increase in ROS formation as well as LPO and GSH depletion. Moreover, mitochondrion seems to be targets of TZ-induced toxicity. The severe hepatotoxicity of TZ in enzyme-induced rats suggests the potential role of reactive intermediates. The present study proposes the protective effect of NAC and/or taurine against TZ-induced cellular injury, probably through their radical scavenging properties and effects on mitochondria.
ISSN:0091-150X
1573-9031
DOI:10.1007/s11094-018-1724-6