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Quantitative X-ray microanalysis of alveolar macrophages after long-term treatment with amiodarone
1Department of Anatomy, West Virginia University Health Sciences Center, Morgantown 26506.
Abstract:
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.
Insights
Long-term amiodarone treatment alters iodine distribution in rat alveolar macrophages, concentrating in nuclei and lamellar bodies. This drug also affects cellular ion balance, decreasing potassium and increasing sodium.
Area of Science:
- Pulmonary toxicology
- Cellular biology
- Pharmacology
Background:
- Amiodarone, an antiarrhythmic drug, can induce pulmonary toxicity.
- Alveolar macrophages accumulate amiodarone and its metabolites.
- Lipid-rich lamellar bodies form in macrophages of amiodarone-treated animals.
Purpose of the Study:
- To investigate the long-term effects of amiodarone on iodine distribution within alveolar macrophages.
- To examine changes in cellular cation concentrations during prolonged amiodarone treatment.
Main Methods:
- X-ray microanalysis of freeze-dried cryosections of rat alveolar macrophages.
- Monitoring iodine distribution after 1 and 9 weeks of amiodarone treatment.
Main Results:
- Iodine concentrations increased in macrophage nuclei over time, reaching levels similar to lamellar bodies after 9 weeks.
- Cellular potassium levels decreased, while sodium levels increased with amiodarone treatment duration.
- These cation changes suggest amiodarone and its metabolite, desethylamiodarone, inhibit Na-K-ATPase, altering ion transport.
Conclusions:
- Prolonged amiodarone exposure leads to significant redistribution of iodine within alveolar macrophages.
- Amiodarone treatment disrupts macrophage ion homeostasis, likely via Na-K-ATPase inhibition.
- Understanding these cellular effects is crucial for managing amiodarone-induced pulmonary toxicity.