Cytotoxicity of amiodarone in cultured human endothelial cells

Cardiovascular Drugs and Therapy
B BaudinJ Giboudeau

Abstract

As damage to the pulmonary vascular endothelium may be responsible for the lung toxicity of amiodarone, we evaluated the cytolytic toxicity of the drug in cultures of endothelial cells. Cells were cultured from human umbilical cord veins. Amiodarone caused a vacuolization of the cells with liberation of both lactate dehydrogenase (LDH) and angiotensin-converting enzyme (ACE) in the culture medium. These effect were both concentration and time dependent, and were correlated between them. The first toxic effects were shown as soon as 2 hours after contact with the drug and at 0.1 mg/ml, a concentration that can be reached in plasma of amiodarone-treated patients. A decrease of ACE activity in the cells was delayed to 24 hours and only with the 10 mg/ml concentration. This event correlated with cell death and detachment from the extracellular matrix. LDH increases corresponded to its isoenzymes 3 and 4. These data support the hypothesis of a direct toxic effect of amiodarone on the endothelium and show the need for evaluating LDH, total activity and isoenzymic profile, and ACE determinations in the plasma of patients treated with amiodarone for ischemic heart disease or arrhythmia.

References

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Citations

Jun 15, 2011·Cardiovascular Toxicology·Sathish Kumar ManeyC C Kartha
Sep 17, 2004·Endothelium : Journal of Endothelial Cell Research·Agnès MaillouxBruno Baudin
Dec 15, 2015·Cardiovascular Toxicology·G S AjithkumarC C Kartha
Jun 30, 2009·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Mohammed Reza MoussavianMartin Karl Schilling
Oct 13, 2011·Journal of Applied Toxicology : JAT·Seref AlpsoyAsuman Gedikbasi
Sep 17, 2016·Critical Care Medicine·Marco WitkowskiCarsten Skurk
Apr 5, 2007·Nature Protocols·Bruno BaudinMichel Vaubourdolle
Dec 3, 2020·Journal of Cardiothoracic and Vascular Anesthesia·Eric T FeduskaJordan E Goldhammer

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