Neutrality of amiodarone on the initiation and propagation of membrane lipid peroxidation.
Amiodarone is an iodinated benzofuran derivative largely used as an antiarrhythmic. Owing to the sensitivity of heart tissue to radicals, amiodarone was assayed for putative effects on lipid peroxidation studied in liposomes of soybean phosphatidylcholine and of bovine heart mitochondrial lipids used as model systems. Lipid peroxidations were initiated with Fe2+/ascorbic acid, and with peroxyl radicals generated from the azocompounds, AAPH and AMVN. These assays were carried out by following the quenching of the fluorescent probe cis-parinaric acid and by monitoring oxygen consumption. It has been ascertained that amiodarone does not protect or potentiate significantly the lipid peroxidation both lipidic systems. To fully ascertain the neutral behaviour of amiodarone in the lipid peroxidation process, the degradation of phospholipid acyl chains has been checked by GLC. These data confirm 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 possible that the drug causes limited conformational and biophysical alterations in membrane phospholipid bilayers that can affect the process of peroxidation. Therefore, it is concluded that the therapeutic effects and benefits as a heart antiarrhythmic agent are independent of lipid peroxidation processes. Furthermore, the interaction of the drug with lipid bilayers does not induce significant conformational perturbations that could significantly favour or depress the peroxidation process.
Mansani
F P
FP
Departamento de Bioquímica da Universidade Federal do Paraná, Curitiba, PR, Brasil.
Dinis
T C
TC
Carnieri
E G
EG
Madeira
V M
VM
D000215:Acylation; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002417:Cattle; D005453:Fluorescence; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes; D008563:Membrane Lipids / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013025:Glycine max
D000889:Anti-Arrhythmia Agents; D008081:Liposomes; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D000638:Amiodarone