title: Cytotoxicity effects of amiodarone on cultured cells.
abstract: Amiodarone is a potent anti-arrhythmic drug used for the treatment of cardiac arrhythmias. Although, the effects of amiodarone are well characterized on post-ischemic heart and cardiomyocytes, its toxicity on extra-cardiac tissues is still poorly understood. To this aim, we have monitored the cytotoxicity effects of this drug on three cultured cell lines including hepatocytes (HepG2), epithelial cells (EAhy 926) and renal cells (Vero). We have investigated the effects of amiodarone on (i) cell viabilities, (ii) heat shock protein expressions (Hsp 70) as a parameter of protective and adaptive response and (iii) oxidative damage.Our results clearly showed that amiodarone inhibits cell proliferation, induces an over-expression of Hsp 70 and generates significant amount of reactive oxygen species as measured by lipid peroxidation occurrence. However, toxicity of amiodarone was significantly higher in renal and epithelial cells than in hepatocytes. Vitamin E supplement restores the major part of cell mortalities induced by amiodarone showing that oxidative damage is the predominant toxic effect of the drug.Except its toxicity for the cardiac system, our findings demonstrated that amiodarone can target other tissues. Therefore, kidneys present a high sensibility to this drug which may limit its use with subjects suffering from renal disorders.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Rue Avicenne, 5019 Monastir, Tunisia. emnagol@yahoo.fr
authors.forename: Emna El
authors.initials: EE
authors.lastname: Golli-Bennour
authors.forename: Amel
authors.initials: A
authors.lastname: Bouslimi
authors.forename: Olfa
authors.initials: O
authors.lastname: Zouaoui
authors.forename: Safa
authors.initials: S
authors.lastname: Nouira
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Achour
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000889:Anti-Arrhythmia Agents; D018840:HSP70 Heat-Shock Proteins; D000638:Amiodarone