Toxicity of amiodarone on mouse pulmonary endothelial cells cultured with or without alveolar macrophages.
This study was designed to specify the toxicity of amiodarone toward mouse pulmonary endothelial cells in comparison with that of another cationic amphiphilic drug, i.e., mianserin. These examinations were performed in the absence and presence of mouse alveolar macrophages under transmembrane co-culture or in direct contact with the endothelial cells to assess the contribution of macrophages to the toxicities toward the endothelial cells. As a result of 24-hr treatment, amiodarone caused a decrease in cell viability, in H(+)-ATPase, acid sphingomyelinase, and acid phospholipase A2 activities, and in neutral red uptake, and an increase in permeability of the endothelial cells. Because the magnitude of changes in the endothelial cells was the greatest under direct contact with macrophages, and was the mildest without macrophages, macrophages were considered to enhance the toxicity of amiodarone toward the endothelial cells. Additionally, the toxic effect of amiodarone on the cells was depressed by pretreatment of them with docosahexaenoic acid (DHA) or alpha-tocopherol for 2 days and co-treatment with these agents for 1 day, but not with prednisolone or indomethacin co-treatment. DHA and alpha-tocopherol protected endothelial cells from the toxicity of amiodarone. The effect was more potent for DHA than alpha-tocopherol.
Futamura
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Y
Department of Pharmacology, Toho University School of Medicine, Tokyo, Japan.
D000638:Amiodarone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007213:Indomethacin / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D008803:Mianserin / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D011239:Prednisolone / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D014810:Vitamin E; D008803:Mianserin; D004281:Docosahexaenoic Acids; D011239:Prednisolone; D000638:Amiodarone; D007213:Indomethacin