Shohreh Taziki
1,2, Mohammad Reza Sattari
3,4, Siavoush Dastamalchi
5, Mohammad Ali Eghbal
6,3*1 Ischemic Disorders Research Center,Golestan University of Medical Sciences, Gorgan, Iran.
2 Students’ Research Committee, Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran.
3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Neurosciences Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Author: Department of Pharmacology and Toxicology, Faculty of pharmacy, Tabriz university of Medical Sciences, Tabriz, Iran Email m.a.eghbal@hotmail.com
Abstract
Purpose: Amitriptyline,
one of the commonly used tricyclic antidepressants, caused rare but severe
hepatotoxicity in patients who received it continuously. Previous findings
showed that the intermediate metabolites of amitriptyline produced by CYP450
are involved in hepatic injury. Melatonin is an antiaging and antioxidant
hormone synthesized from pineal gland. The aim of present study was to evaluate
the protective role of melatonin in an in vitro model of isolated rat
hepatocytes.
Methods: Markers such as cell viability, reactive
oxygen species formation, lipid peroxidation, mitochondrial membrane potential,
and hepatocytes glutathione content were evaluated every 60 minutes for 180
minutes.
Results: Present results indicated that administration of 1mM of
melatonin effectively reduced the cell death, ROS formation and lipid
peroxidation, mitochondrial membrane potential collapse, and reduced cellular
glutathione content caused by amitriptyline.
Conclusion: Our results indicated that melatonin is an
effective antioxidant in preventing amitriptyline-induced hepatotoxicity. We
recommend further in vivo animal and clinical trial studies on the
hepatoprotective effects of melatonin in patients receiving amitriptyline.