Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis
Joint Authors
Urbina, Julio A.
Macedo-Silva, Sara Teixeira de
de Souza, Wanderley
Oliveira Silva, Thais Larissa Araújo de
Rodrigues, Juliany Cola Fernandes
Source
Molecular Biology International
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-06-13
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Amiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania.
In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes.
The IC50 values were 4.21 and 0.46 μM against promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage.
We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm) and to an increase in the production of reactive oxygen species, in a dose-dependent manner.
Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes.
Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity.
Taken together, our results indicate that AMIO is a potent inhibitor of L.
amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy.
American Psychological Association (APA)
Macedo-Silva, Sara Teixeira de& Oliveira Silva, Thais Larissa Araújo de& Urbina, Julio A.& de Souza, Wanderley& Rodrigues, Juliany Cola Fernandes. 2011. Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis. Molecular Biology International،Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-505447
Modern Language Association (MLA)
Macedo-Silva, Sara Teixeira de…[et al.]. Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis. Molecular Biology International No. 2011 (2011), pp.1-12.
https://search.emarefa.net/detail/BIM-505447
American Medical Association (AMA)
Macedo-Silva, Sara Teixeira de& Oliveira Silva, Thais Larissa Araújo de& Urbina, Julio A.& de Souza, Wanderley& Rodrigues, Juliany Cola Fernandes. Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis. Molecular Biology International. 2011. Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-505447
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-505447