Amiodarone Induces Two Different Types of Disorders in Mouse Alveolar Macrophages.

Abstract

ABSTRACT-It has been reported that amiodarone induces disorders of alveolar macrophages and pul monary fibrosis, but the mechanism is not well-understood. This study was performed to elucidate the toxic mechanism from the standpoint of cellular function. Using alveolar macrophages obtained from a male Slc:ICR mouse, several injuries caused by amiodarone were compared to those caused by amantadine and mianserin as cationic amphiphilic drugs (CADs). As parameters for the drug effects, H+-ATPase and acid sphingomylinase activities, cellular pH, cytokine and prostaglandin releases, phagocytosis and neutral red uptake were measured. Amiodarone decreased H+-ATPase activity initially and subsequently increased cellular pH and decreased acid sphingomyelinase activity. These changes, which were also observed with amantadine and mianserin, were considered to be CAD-related. Amiodarone increased cytokine and prostaglandin releases and suppressed neutral red uptake and phagocytosis. These changes, being not induced by amantadine and mianserin, were considered to be specific for amiodarone. The above data suggest that amiodarone has two types of toxic effects on alveolar macrophages.

Amiodarone and Bepridil Inhibit Anthrax Toxin Entry into Host Cells

“…One-way ANOVA analysis indicated that differences in time to death were significant (P Ͻ 0.0001). Further statistical analysis was performed using the Tukey test to determine whether individual treatment groups were significantly different from the control group (shown in Conflicting data exist as to whether amiodarone is lysosomotropic or whether the tertiary amine present in amiodarone neutralizes lysosomal pH (4,9,19,20,23,25,43). Interestingly, our findings differ from those of Baritussio et al who reported that 10 M amiodarone did not block DT activity in rabbit alveolar macrophages (4).…”

“…Interestingly, our findings differ from those of Baritussio et al who reported that 10 M amiodarone did not block DT activity in rabbit alveolar macrophages (4). In contrast, Futamura reported that amiodarone inhibits endosomal acidification and cellular pH using fluorescein isothiocyanate-dextran or acridine orangebased fluorescence assays (19,20). These effects were seen as early as 30 min postexposure, consistent with our data in which drugs are added immediately before toxin.…”

“…These effects were seen as early as 30 min postexposure, consistent with our data in which drugs are added immediately before toxin. Furthermore, both Futamura and Quaglino et al reported differential cellular effects of amiodarone based on its cationic, amphiphilic, or unique properties (19,43). Thus, it may be possible to identify analogs that retain antitoxic activity while removing antiarrythmic and/or toxic properties.…”

Διερεύνηση των μηχανισμών του κυτταρικού stress κατόπιν επιδράσεως χημειοθεραπευτικών παραγόντων ρυθμιστών των αντιδράσεων υπερευαισθησίας και φαρμάκων του γαστρεντερικού

“…!%,( $ % + , Ca 2+ "%! + (Kodama et al 1997) (Futamura 1997, Pozniakovsky et al 2005. Drvota et al 1995, Kodama et al 1999.…”

Συγκριτική Μελέτη Επίδρασης Χορήγησης Αμιωδαρόνης Και Δρονεδαρόνης Στον Πνεύμονα

“…Από έρευνες που πραγματοποιήθηκαν τόσο in vivo όσο και in vitro, έχουν προταθεί αρκετές θεωρίες για τους παθογενετικούς μηχανισμούς της τοξικότητας της αμιωδαρόνης, οι οποίοι περιλαμβάνουν: α) μεταβολές στις ιδιότητες των μεμβρανών (101,127), β) αύξηση της συγκέντρωσης του ενδοκυττάριου ελεύθερου ασβεστίου (94,97,128), γ) παραγωγή ελεύθερων ριζών (94. 129), δ) φωσφολιπίδωση του πνεύμονα (94,97,101,, ε) ανοσολογικούς μηχανισμούς (94,101,127,132), και στ) απευθείας τοξική δράση του φαρμάκου (94,97,101,121).…”