Jpn. J. Pharmacol. 74 (1), 21-28 (1997)

Amiodarone Induces Two Different Types of Disorders in Mouse Alveolar Macrophages

Yoshihiro Futamura

Department of Pharmacology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143, Japan

Abstract: It has been reported that amiodarone induces disorders of alveolar macrophages and pulmonary fibrosis, but the mechanism is not well-understood. This study was performed to elucidate the toxic mechanism from the 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 amphiphilic drugs (CADs). As parameters for the drug effects, H+-ATPase and acid sphingomyelinase activities, cellular pH, cytokine and prostaglandin releases, phagocytosis and neutral red uptake were measured. Amiodarone decreased H+-ATPase activity initially and subsequently increased cellular pH and decreased acid sphingomyelinase activity. These changes, which were also observed with amantadine and mianserin, were considered to be CAD-related. Amiodarone increased cytokine and prostaglandin releases and suppressed neutral red uptake and phagocytosis. These changes, being not induced by amantadine and mianserin, were considered to be specific for amiodarone. The above data suggest that amiodarone has two types of toxic effects on alveolar macrophages.

Keywords: Alveolar macrophage, Amiodarone, Cationic amphiphilic drug, H+-ATPase, Pulmonary toxicity

Copyrightę The Japanese Pharmacological Society 1997

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