Cytotoxicity of amiodarone in cultured human endothelial cells.
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.
Baudin
B
B
Laboratoire de Biochimie A, Hôpital Saint-Antoine, Paris, France.
Bénéteau-Burnat
B
B
Giboudeau
J
J
D000638:Amiodarone / Q000633:toxicity*; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D007703:Peptidyl-Dipeptidase A; D000638:Amiodarone