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Abstract
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. 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. 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. 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.
Highlights
Melatonin is produced in the vertebrate pineal gland, the retina and possibly some other organs
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
We investigated, for the first time, the protective roles of melatonin against cytotoxicity induced by amitriptyline towards freshly isolated rat hepatocytes
Summary
Melatonin is produced in the vertebrate pineal gland, the retina and possibly some other organs This hormone plays several physiological roles such as regulation of sleep. There are many reports that melatonin’s antioxidant action contributes to the protection of the organism from carcinogenesis and neurodegenerative disorders It acts as a potent antioxidant by mechanisms such as stimulation of antioxidant enzymes, increasing the efficiency of mitochondrial oxidative phosphorylation and reducing free radical generation and direct free radical scavenging.[1,2,3,4] There are many reports on melatonin’s protective effects against different chemicals-induced hepatotoxicity.[5,6]. The effect of amitriptylin on hepatocyte mitochondria was studied
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