Role of phospholipase A inhibition in amiodarone pulmonary toxicity in rats.
Amiodarone is effective in the treatment of ventricular and supraventricular arrhythmias. In man its clinical use is associated with the accumulation of phospholipid-rich multilamellar inclusions in various tissues including lung, liver and others. This report presents evidence showing that amiodarone is a potent inhibitor of lysosomal phospholipase A from rat alveolar macrophages, J-744 macrophages and rat liver. When compared with other cationic amphiphilic agents which are known to produce phospholipidosis, amiodarone is one of the most potent inhibitors yet discovered. The subcellular localization of amiodarone has been determined in lung and its distribution was consistent with a lysosomal localization. It is hypothesized that amiodarone causes cellular phospholipidosis by concentrating in lysosomes and inhibiting phospholipid catabolism.
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D051381:Rats
D001572:Benzofurans; D010740:Phospholipases; D010741:Phospholipases A; D000638:Amiodarone