X-ray microanalysis of cultured alveolar macrophages with phospholipidosis.
When administered to humans and animals, the iodine-containing drug amiodarone can cause pulmonary toxicity. As part of the pulmonary response to amiodarone, the drug and its principal metabolite, desethylamiodarone, accumulate in alveolar macrophages. Little is known about the susceptibility of lungs with preexisting damage to amiodarone administration. A number of chemicals can cause pulmonary phospholipidosis in humans and animals. To study the effect of a preexisting phospholipidosis on the intracellular accumulation of amiodarone and desethylamiodarone, rats were treated with chlorphentermine to induce a phospholipidosis in alveolar macrophages. The cells were recovered from the lungs by pulmonary lavage and placed in cell culture. They were then exposed to the same concentration of either amiodarone or desethylamiodarone. The intracellular distribution of each drug was quantified by measuring the associated iodine signal using X-ray microanalysis of freeze-dried cryosections of cells. Both drugs accumulated in lipid-rich amorphous bodies which correspond to lysosomally derived lamellar structures observed in conventional plastic sections. The level of desethylamiodarone exceeded that of amiodarone in the amorphous bodies. With both drugs, a higher concentration of iodine was present at the outer edges of the amorphous bodies compared to that in the center core. This suggests that the drugs are unable to freely penetrate the performed structures. By monitoring the concentrations of sodium and potassium ions within the nucleus, it was determined that chlorphentermine treatment disrupted the ionic distribution in the cells. Exposure to amiodarone, but not desethylamiodarone, resulted in further changes in sodium and potassium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
P
P
Department of Physiology, West Virginia University Health Sciences Center, Morgantown 26506.
Kirk
R G
RG
Reasor
M J
MJ
D000638:Amiodarone / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002745:Chlorphentermine / Q000494:pharmacology; D004577:Electron Probe Microanalysis; D005612:Freeze Drying; D005629:Frozen Sections; D002479:Inclusion Bodies / Q000737:chemistry / Q000648:ultrastructure; D008064:Lipidoses / Q000378:metabolism* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D011188:Potassium / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000032:analysis / Q000378:metabolism
D010743:Phospholipids; D012964:Sodium; C036116:desethylamiodarone; D000638:Amiodarone; D002745:Chlorphentermine; D011188:Potassium