Quantitative X-ray microanalysis of alveolar macrophages after long-term treatment with amiodarone
Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to formation of lipid-rich lamellar bodies in amiodarone-treated animals. Amiodarone and several of its metabolites accumulate in the cell. Previously...
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Published in | Experimental and molecular pathology Vol. 52; no. 1; pp. 122 - 131 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
01.02.1990
Elsevier |
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Abstract | Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to formation of lipid-rich lamellar bodies in amiodarone-treated animals. Amiodarone and several of its metabolites accumulate in the cell. Previously, we have reported that the technique of X-ray microanalysis is useful in monitoring the distribution of iodine in freeze-dried cryosections of alveolar macrophages from Fischer 344 rats 24 hr after a single dose of amiodarone. In the present study, we examine the effects of longer term amiodarone treatment of 1 or 9 weeks. Substantial changes in iodine distribution occur in the cells with increasing length of drug treatment. High concentrations of iodine are found early in the lamellar bodies. The iodine levels in the nuclei slowly increase with the length of treatment, and after 9 weeks of treatment, approach those found in the lamellar bodies. It is possible that this accumulation of iodine in the nuclei is due to the presence of polar metabolites. In addition, the potassium concentration in the cell decreases and the sodium increases with treatment duration. These changes in cations are most likely due to altered ion transport in the macrophages by the inhibition of membrane NaK-ATPase by the drug and its principal metabolite, desethylamiodarone. |
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AbstractList | Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to formation of lipid-rich lamellar bodies in amiodarone-treated animals. Amiodarone and several of its metabolites accumulate in the cell. Previously, we have reported that the technique of X-ray microanalysis is useful in monitoring the distribution of iodine in freeze-dried cryosections of alveolar macrophages from Fischer 344 rats 24 hr after a single dose of amiodarone. In the present study, we examine the effects of longer term amiodarone treatment of 1 or 9 weeks. Substantial changes in iodine distribution occur in the cells with increasing length of drug treatment. High concentrations of iodine are found early in the lamellar bodies. The iodine levels in the nuclei slowly increase with the length of treatment, and after 9 weeks of treatment, approach those found in the lamellar bodies. It is possible that this accumulation of iodine in the nuclei is due to the presence of polar metabolites. In addition, the potassium concentration in the cell decreases and the sodium increases with treatment duration. These changes in cations are most likely due to altered ion transport in the macrophages by the inhibition of membrane NaK-ATPase by the drug and its principal metabolite, desethylamiodarone. Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to formation of lipidrich lamellar bodies in amiodarone-treated animals. Amiodarone and several of its metabolites accumulate in the cell. Previously, we have reported that the technique of X-ray microanalysis is useful in monitoring the distribution of iodine in freeze-dried cryosections of alveolar macrophages from Fischer 344 rats 24 hr after a single dose of amiodarone. In the present study, we examine the effects of longer term amiodarone treatment of 1 or 9 weeks. Substantial changes in iodine distribution occur in the cells with increasing length of drug treatment. High concentrations of iodine are found early in the lamellar bodies. The iodine levels in the nuclei slowly increase with the length of treatment, and after 9 weeks of treatment, approach those found in the lamellar bodies. It is possible that this accumulation of iodine in the nuclei is due to the presence of polar metabolites. In addition, the potassium concentration in the cell decreases and the sodium increases with treatment duration. These changes in cations are most likely due to altered ion transport in the macrophages by the inhibition of membrane Na-K-ATPase by the drug and its principal metabolite, desethylamiodarone. |
Author | Reasor, Mark J. Lee, Ping Kirk, R.Gary |
Author_xml | – sequence: 1 givenname: R.Gary surname: Kirk fullname: Kirk, R.Gary organization: Department of Anatomy, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506 USA – sequence: 2 givenname: Ping surname: Lee fullname: Lee, Ping organization: Department of Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506 USA – sequence: 3 givenname: Mark J. surname: Reasor fullname: Reasor, Mark J. organization: Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506 USA |
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Cites_doi | 10.1007/BF01868938 10.1016/0002-8703(86)90473-4 10.1161/01.CIR.65.4.819 10.1164/ajrccm/137.3.510 10.1016/0041-008X(89)90061-6 10.1056/NEJM198407193110308 10.1136/jcp.40.4.418 10.7326/0003-4819-97-6-839 10.1083/jcb.96.5.1389 10.1111/j.1365-2133.1984.tb04660.x 10.1159/000115456 10.1016/0014-4800(88)90006-8 10.1016/0304-3991(76)90049-8 |
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Keywords | Drug Sodium Toxicity Animal Lung Microanalysis X ray Potassium Quantitative analysis Iodine Macrophage |
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Neurol. doi: 10.1159/000115456 contributor: fullname: LeMaire – volume: 49 start-page: 339 year: 1988 ident: 10.1016/0014-4800(90)90064-K_BIB5 article-title: Iodine in rat alveolar macrophages following aminodarone treatment: Quantitative x-ray microanalysis publication-title: Exp. Mol. Pathol. doi: 10.1016/0014-4800(88)90006-8 contributor: fullname: Kirk – volume: 59 start-page: 449 year: 1986 ident: 10.1016/0014-4800(90)90064-K_BIB1 article-title: Amiodarone pulmonary toxicity: Clinical and subclinical features publication-title: Q. J. Med. contributor: fullname: Adams – volume: 1 start-page: 317 year: 1976 ident: 10.1016/0014-4800(90)90064-K_BIB14 article-title: Quantitative electron probe microanalysis of biological thin sections: Method and validation publication-title: Ultramicroscopy doi: 10.1016/0304-3991(76)90049-8 contributor: fullname: Shuman |
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Snippet | Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to... |
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SubjectTerms | 550501 - Metabolism- Tracer Techniques Amiodarone - pharmacology ANIMAL CELLS ANIMALS BASIC BIOLOGICAL SCIENCES BIOLOGICAL ACCUMULATION Biological and medical sciences CARDIOVASCULAR AGENTS CHEMICAL ANALYSIS CONNECTIVE TISSUE CELLS Cryopreservation DRUGS ELECTRON MICROPROBE ANALYSIS Electron Probe Microanalysis ELEMENTS HALOGENS IODINE Iodine - analysis MACROPHAGES Macrophages - analysis Macrophages - drug effects Macrophages - ultrastructure Male MAMMALS Medical sciences METABOLISM METABOLITES MICROANALYSIS Microscopy, Electron NONMETALS PHAGOCYTES Potassium - analysis Pulmonary Alveoli - analysis Pulmonary Alveoli - cytology Pulmonary Alveoli - ultrastructure RATS Rats, Inbred F344 RODENTS Sodium - analysis SOMATIC CELLS Time Factors Toxicology VASODILATORS VERTEBRATES |
Title | Quantitative X-ray microanalysis of alveolar macrophages after long-term treatment with amiodarone |
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