Neutrality of amiodarone on the initiation and propagation of membrane lipid peroxidation

Amiodarone is an iodinated benzofuran derivative largely used as an antiarr hythmic. Owing to the sensitivity of heart tissue to radicals, amiodarone w as assayed for putative effects on lipid peroxidation studied in liposomes of soybean phosphatidylcholine and of bovine heart mitochondrial lipids use d as model systems. Lipid peroxidations were initiated with Fe2+/ascorbic a cid, and with peroxyl radicals generated from the azocompounds, AAPH and AM VN. These assays were carried out by following the quenching of the fluores cent probe cis-parinaric acid and by monitoring oxygen consumption. It has been ascertained that amiodarone does not protect or potentiate significant ly the lipid peroxidation in both lipidic systems. To fully ascertain the n eutral behaviour of amiodarone in the lipid peroxidation process, the degra dation of phospholipid acyl chains has been checked by GLC. These data conf irm that amiodarone does not protect or potentiate lipid peroxidation to a significant extent. It is concluded that the limited effects of amiodarone might be related only indirectly with the lipid peroxidation. It is possibl e that the drug causes limited conformational and biophysical alterations i n membrane phospholipid bilayers that can affect the process of peroxidatio n. Therefore, it is concluded that the therapeutic effects and benefits as a heart antiarrhythmic agent are independent of lipid peroxidation processe s. Furthermore, the interaction of the drug with lipid bilayers does not in duce significant conformational perturbations that could significantly favo ur or depress the peroxidation process. Copyright (C) 1999 John Wiley & Son s, Ltd.