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

  • Aziz Eftekhari
  • Elham Ahmadian
  • Yadollah Azarmi
  • Alireza Parvizpur
  • Javad Khalili Fard
  • Mohammad Ali Eghbal
Article
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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.

Keywords

thioridazine hepatotoxicity formation of reactive oxygen species oxidative stress 

Notes

Acknowledgments

This is a report of the database from thesis entitled “Evaluation of the Mechanisms of Hepatic Injuries Induced by Antipsychotic Drugs” (Grant no. 101/93) registered in “Drug Applied Research Center.”

Conflict of Interest

The authors declare that there are no conflicts of interest associated with this work.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Aziz Eftekhari
    • 1
    • 2
    • 3
  • Elham Ahmadian
    • 1
    • 2
  • Yadollah Azarmi
    • 2
    • 3
  • Alireza Parvizpur
    • 2
    • 3
  • Javad Khalili Fard
    • 2
    • 3
  • Mohammad Ali Eghbal
    • 2
    • 3
  1. 1.Pharmacology and Toxicology DepartmentMaragheh University of Medical SciencesMaraghehIran
  2. 2.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Pharmacology and Toxicology Department, School of PharmacyTabriz University of Medical SciencesTabrizIran

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