Differential susceptibilities of isolated hamster lung cell types to amiodarone toxicity |
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Authors: | Bolt M W Racz W J Brien J F Bray T M Massey T E |
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Institution: | Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada. |
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Abstract: | Treatment of cardiac dysrhythmias with the iodinated benzofuran derivative amiodarone (AM) is limited by pulmonary toxicity. The susceptibilities of different lung cell types of male Golden Syrian hamsters to AM-induced cytotoxicity were investigated in vitro. Bronchoalveolar lavage and protease digestion to release cells, followed by centrifugal elutriation and density gradient centrifugation, resulted in preparations enriched with alveolar macrophages (98%), alveolar type II cells (75-85%), and nonciliated bronchiolar epithelial (Clara) cells (35-50%). Alveolar type II cell and Clara cell preparations demonstrated decreased viability (by 0.5% trypan blue dye exclusion) when incubated with 50 microM AM for 36 h, and all AM-treated cell preparations demonstrated decreased viability when incubated with 100 or 200 microM AM. Based on a viability index ((viability of AM-treated cells/viability of controls) x 100%), the Clara cell fraction was significantly (p<0.05) more susceptible than all of the other cell types to 50 microM AM. However, AM cytotoxicity was greatest (p<0.05) in alveolar macrophages following incubation with 100 or 200 microM AM. There was no difference between any of the enriched cell preparations in the amount of drug accumulated following 24 h of incubation with 50 microM AM, whereas alveolar macrophages accumulated the most drug during incubation with 100 microM AM. Thus, the most susceptible cell type was dependent on AM concentration. AM-induced cytotoxicity in specific cell types may initiate processes leading to inflammation and pulmonary fibrosis. |
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