Archives of Pharmacal Research

, Volume 40, Issue 11, pp 1296–1313 | Cite as

In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity

  • Elham Ahmadian
  • Aziz Eftekhari
  • Javad Khalili Fard
  • Hossein Babaei
  • Alireza Mohajjel Nayebi
  • Daryoush Mohammadnejad
  • Mohammad Ali Eghbal
Research Article

Abstract

Even though citalopram is commonly used in psychiatry, there are several reports on its toxic effects. So, the current study was designed to elucidate the mechanisms of cytotoxic effects of in vitro and in vivo citalopram treatment on liver and the following cytolethal events. For in vitro experiments, freshly isolated rat hepatocytes were exposed to citalopram along with/without various agents. To do in vivo studies liver function enzyme assays and histological examination were performed. In the in vitro experiments, citalopram (500 µM) exposure demonstrated cell death, a marked elevation in ROS formation, mitochondrial potential collapse, lysosomal membrane leakiness, glutathione (GSH) depletion and lipid peroxidation. In vivo biochemistry panel assays for liver enzymes function (AST, ALT and GGTP) and histological examination confirmed citalopram (20 mg/kg)-induced damage. citalopram-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, MPT pore sealing agents, endocytosis inhibitors, ATP generators and CYP inhibitors. Either enzyme induction or GSH depletion were concomitant with augmented citalopram-induced damage both in vivo and in vitro which were considerably ameliorated with antioxidants and CYP inhibitors. In conclusion, it is suggested that citalopram hepatotoxicity might be a result of oxidative hazard leading to mitochondrial/lysosomal toxic connection and disorders in biochemical markers which were supported by histomorphological studies.

Keywords

Citalopram Antioxidants Cytotoxicity Mitochondrial/lysosomal dysfunction Oxidative stress 

Notes

Acknowledgments

The authors would like to thank Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran, for providing technical facilities. This is a report of a database from thesis entitled “Evaluation of the mechanisms of hepatic injuries induced by antidepressant drugs” registered and funded by a grant (Grant number: 77/93) from the Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran. The authors are also thankful to the University’s “Students’ Research Committee” for providing technical supports to the study.

Compliance of ethical standard

Conflict of interest

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

Funding information

Drug applied research center (Grant number: 77/93).

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Copyright information

© The Pharmaceutical Society of Korea 2016

Authors and Affiliations

  • Elham Ahmadian
    • 1
    • 2
    • 3
    • 4
  • Aziz Eftekhari
    • 3
    • 4
  • Javad Khalili Fard
    • 3
    • 4
  • Hossein Babaei
    • 2
    • 3
  • Alireza Mohajjel Nayebi
    • 3
  • Daryoush Mohammadnejad
    • 2
  • Mohammad Ali Eghbal
    • 2
    • 3
  1. 1.Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Department of Pharmacology and Toxicology, Faculty of PharmacyTabriz University of Medical SciencesTabrizIran
  4. 4.Students’ Research CommitteeTabriz University of Medical SciencesTabrizIran

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