Life cell imaging of amiodarone sequestration into lamellar bodies of alveolar type II cells.

Autor: Haller T; Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: Thomas.Haller@i-med.ac.at., Jesacher A; Institute of Biomedical Physics, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: Alexander.Jesacher@i-med.ac.at., Hidalgo A; Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, Madrid, Spain. Electronic address: Alberto.hidalgo@charite.de., Schmidt C; Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2024 Feb; Vol. 94, pp. 105733. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1016/j.tiv.2023.105733
Abstrakt: Amiodarone is widely used to treat cardiac arrhythmias and is very effective in preventing these disorders. However, its use is limited by a wide range of adverse effects, mainly affecting the lungs, and ranging from mild shortness of breath to pulmonary fibrosis. Amiodarone has been shown to accumulate strongly in lung tissue, exceeding its plasma concentration by a hundredfold. However, the site of accumulation and the mechanisms of transport are not fully understood. In this study, we used live cell imaging of primary rat alveolar type II cells to show that amiodarone specifically accumulates in large amounts in lamellar bodies, the surfactant storage organelles. Fluorescence imaging and correlation, and colocalization studies combined with confocal Raman microscopy identified these organelles as a major target for sequestration. Accumulation was rapid, on the order of a few hours, while storage was much more persistent. Partial uptake was observed in chemically fixed, dead cells, or cells treated with bafilomycin A1. Not only was uptake pH dependent, but intraluminal pH, measured with lysosomotropic pH sensitive dyes, was also affected. From these observations and from the physicochemical properties of amiodarone, we propose that passive diffusion, ion-trapping and lipophilic interactions are the main mechanisms for intracellular bioaccumulation. Furthermore, we demonstrate that measurement of amiodarone autofluorescence is highly useful for tracking cellular uptake and sequestration.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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