Cytotoxicity effects of amiodarone on cultured cells
Emna El Golli-Bennour1, Amel Bouslimi, Olfa Zouaoui
1Laboratory of Research on Biologically Compatible Compounds, Rue Avicenne, 5019 Monastir, Tunisia. emnagol@yahoo.fr
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.
Insights
Amiodarone, an anti-arrhythmic drug, harms kidney and epithelial cells more than liver cells by causing oxidative damage. Vitamin E may mitigate this toxicity, suggesting careful use in patients with kidney issues.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Amiodarone is a key anti-arrhythmic medication.
- Its cardiac effects are known, but extra-cardiac toxicity is unclear.
Purpose of the Study:
- To investigate amiodarone's cytotoxicity on non-cardiac cell lines.
- To assess its impact on cell viability, heat shock protein expression, and oxidative damage.
Main Methods:
- Cultured hepatocytes (HepG2), epithelial cells (EAhy 926), and renal cells (Vero) were exposed to amiodarone.
- Cell viability, Hsp 70 expression, and lipid peroxidation were measured.
- The effect of Vitamin E supplementation was evaluated.
Main Results:
- Amiodarone inhibited proliferation and increased Hsp 70 expression across cell lines.
- Significant oxidative damage (lipid peroxidation) was observed.
- Renal and epithelial cells exhibited higher amiodarone toxicity than hepatocytes.
- Vitamin E partially reversed amiodarone-induced cell death.
Conclusions:
- Amiodarone induces oxidative stress and toxicity in extra-cardiac tissues, particularly kidneys and epithelial cells.
- Oxidative damage is a primary mechanism of amiodarone toxicity.
- Kidney function may be compromised by amiodarone use, necessitating caution in patients with renal disorders.
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