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Amiodarone--induced Changes in Surfactant Phospholipids of Rat Lung

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Specialty Pharmacology
Date 1993 Apr 1
PMID 8510769
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Abstract

Amiodarone HCl (AD) is a very effective antiarrhythmic drug, but its use is often associated with serious pulmonary complications. It is shown to induce lung phospholipidosis. Nevertheless, the effects of this drug on pulmonary surfactant which is composed of about 75% phospholipids and which prevents alveolar collapse is not known. Therefore, we have examined the effect of AD on the intra- and extracellular surfactant pools and on the levels of phosphatidylcholine (PC), the primary constituent of pulmonary surfactant. Male Wistar rats were fed AD (175 mg/kg) by oral gavage for three weeks. At the end of the experimental period, the rats were killed, the lungs removed and perfused, and surfactant isolated. Some lungs were prepared for ultrastructural examination. Phospholipid was assayed in the intra- and extracellular surfactant. Amiodarone produced a significant increase in both the intra- and extracellular surfactant phospholipid along with an appreciable change in the phospholipid profile. Also, the drug seemed to increase the number of lamellar inclusions in the surfactant producing type II alveolar cells. These data suggest that administration of AD leads to an increase in the lung surfactant phospholipid levels and lamellar bodies in alveolar type II cells.

References
1.
Wilson B, Jaworski A, Donner M, Lippmann M . Amiodarone-induced pulmonary toxicity in the rat. Lung. 1989; 167(5):301-11. DOI: 10.1007/BF02714959. View

2.
Liu F, Cohen R, Downar E, Butany J, Edelson J, Rebuck A . Amiodarone pulmonary toxicity: functional and ultrastructural evaluation. Thorax. 1986; 41(2):100-5. PMC: 460270. DOI: 10.1136/thx.41.2.100. View

3.
Hostetler K, Giordano J, Jellison E . In vitro inhibition of lysosomal phospholipase A1 of rat lung by amiodarone and desethylamiodarone. Biochim Biophys Acta. 1988; 959(3):316-21. DOI: 10.1016/0005-2760(88)90205-6. View

4.
Kodavanti U, Mehendale H . Amiodarone- and desethylamiodarone-induced pulmonary phospholipidosis, inhibition of phospholipases in vivo, and alteration of [14C]amiodarone uptake by perfused lung. Am J Respir Cell Mol Biol. 1991; 4(4):369-78. DOI: 10.1165/ajrcmb/4.4.369. View

5.
Reasor M . Drug-induced lipidosis and the alveolar macrophage. Toxicology. 1981; 20(1):1-33. DOI: 10.1016/0300-483x(81)90102-5. View