AMIODARONE INDUCES 2 DIFFERENT TYPES OF DISORDERS IN MOUSE ALVEOLAR MACROPHAGES

It has been reported that amiodarone induces disorders of alveolar mac rophages and pulmonary fibrosis, but the mechanism is not well-underst ood. This study was performed to elucidate the toxic mechanism from th e standpoint of cellular function. Using alveolar macrophages obtained from a male Slc:ICR mouse, several injuries caused by amiodarone were compared to those caused by amantadine and mianserin as cationic amph iphilic drugs (CADs). As parameters for the drug effects, H+-ATPase an d acid sphingomylinase activities, cellular pH, cytokine and prostagla ndin releases, phagocytosis and neutral red uptake were measured. Amio darone decreased H+-ATPase activity initially and subsequently increas ed cellular pH and decreased acid sphingomyelinase activity. These cha nges, which were also observed with amantadine and mianserin, were con sidered to be CAD-related. Amiodarone increased cytokine and prostagla ndin releases and suppressed neutral red uptake and phagocytosis. Thes e changes, being not induced by amantadine and mianserin, were conside red to be specific for amiodarone. The above data suggest that amiodar one has two types of toxic effects on alveolar macrophages.