The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone.
Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.
Heath
M F
MF
Costa-Jussà
F R
FR
Jacobs
J M
JM
Jacobson
W
W
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D002479:Inclusion Bodies / Q000473:pathology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000473:pathology; D010713:Phosphatidylcholines / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D010713:Phosphatidylcholines; D010743:Phospholipids; D010740:Phospholipases; D010741:Phospholipases A; D000638:Amiodarone