title: Mechanisms of trazodone-induced cytotoxicity and the protective effects of melatonin and/or taurine toward freshly isolated rat hepatocytes.
abstract: It has been reported that the bioactive intermediate metabolites of trazodone might cause hepatotoxicity. This study was designed to investigate the exact mechanism of hepatocellular injury induced by trazodone as well as the protective effects of taurine and/or melatonin against this toxicity. Freshly isolated rat hepatocytes were used. Trazodone was cytotoxic and caused cell death with LC50 of 300 µm within 2 h. Trazodone caused an increase in reactive oxygen species (ROS) formation, malondialdehyde accumulation, depletion of intracellular reduced glutathione (GSH), rise of oxidized glutathione disulfide (GSSG), and a decrease in mitochondrial membrane potential, which confirms the role of oxidative stress in trazodone-induced cytotoxicity. Preincubation of hepatocytes with taurine prevented ROS formation, lipid peroxidation, depletion of intracellular reduced GSH, and increase of oxidized GSSG. Taurine could also protect mitochondria against trazodone-induced toxicity. Administration of melatonin reduced the toxic effects of trazodone in isolated rat hepatocytes.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Students' Research Committee, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Taziki
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Sattari
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D014196:Trazodone / Q000633:toxicity*
chemical_list: D014151:Anti-Anxiety Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013654:Taurine; D008315:Malondialdehyde; D005978:Glutathione; D008550:Melatonin; D014196:Trazodone
keywords: Hepatocytes; Melatonin; Oxidative Stress; Taurine; Trazodone