In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity
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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.
KeywordsCitalopram Antioxidants Cytotoxicity Mitochondrial/lysosomal dysfunction Oxidative stress
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.
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Conflict of interest
The authors declare that there are no conflicts of interest associated with this work.
Drug applied research center (Grant number: 77/93).
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