Amiodarone may induce lung damage by direct toxicity or indirectly through inflammation. To clarify the mechanism of direct toxicity, we briefly exposed rabbit alveolar macrophages to amiodarone and analyzed their morphology, synthesis, and degradation of dipalmitoylphosphatidylcholine (DPPC); distribution of lysosomal enzymes; and uptake of diphtheria toxin and surfactant protein (SP) A used as tracers of the endocytic pathway. Furthermore, in newborn rabbits, we studied the clearance of DPPC and SP-A instilled into the trachea together with increasing amounts of amiodarone. We found that in vitro amiodarone decreases the surface density of mitochondria and lysosomes while increasing the surface density of inclusion bodies, increases the incorporation of choline into DPPC, modifies the distribution of lysosomal enzymes, and does not affect the uptake and processing of diphtheria toxin but inhibits the degradation of SP-A. In vivo amiodarone inhibits the degradation of SP-A but not of DPPC. We conclude that the acute exposure to amiodarone perturbs the endocytic pathway acting after the early endosomes, alters the traffic of lysosomal enzymes, and interferes with the turnover of SP-A.

Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes / Baritussio, A; Marzini, S; Agostini, M; Alberti, A; Cimenti, C; Bruttomesso, D; Manzato, E; Quaglino, Daniela; Pettenazzo, A.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. - ISSN 1040-0605. - STAMPA. - 281:(2001), pp. 1189-1199.

Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes.

QUAGLINO, Daniela;
2001

Abstract

Amiodarone may induce lung damage by direct toxicity or indirectly through inflammation. To clarify the mechanism of direct toxicity, we briefly exposed rabbit alveolar macrophages to amiodarone and analyzed their morphology, synthesis, and degradation of dipalmitoylphosphatidylcholine (DPPC); distribution of lysosomal enzymes; and uptake of diphtheria toxin and surfactant protein (SP) A used as tracers of the endocytic pathway. Furthermore, in newborn rabbits, we studied the clearance of DPPC and SP-A instilled into the trachea together with increasing amounts of amiodarone. We found that in vitro amiodarone decreases the surface density of mitochondria and lysosomes while increasing the surface density of inclusion bodies, increases the incorporation of choline into DPPC, modifies the distribution of lysosomal enzymes, and does not affect the uptake and processing of diphtheria toxin but inhibits the degradation of SP-A. In vivo amiodarone inhibits the degradation of SP-A but not of DPPC. We conclude that the acute exposure to amiodarone perturbs the endocytic pathway acting after the early endosomes, alters the traffic of lysosomal enzymes, and interferes with the turnover of SP-A.
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1199
Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes / Baritussio, A; Marzini, S; Agostini, M; Alberti, A; Cimenti, C; Bruttomesso, D; Manzato, E; Quaglino, Daniela; Pettenazzo, A.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. - ISSN 1040-0605. - STAMPA. - 281:(2001), pp. 1189-1199.
Baritussio, A; Marzini, S; Agostini, M; Alberti, A; Cimenti, C; Bruttomesso, D; Manzato, E; Quaglino, Daniela; Pettenazzo, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/457458
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