Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis

摘要: Amiodarone (AMIO), the most frequently antiarrhythmic drug used for 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 effects AMIO on proliferation, mitochondrial physiology, ultrastructure Leishmania amazonensis promastigotes intracellular amastigotes. The IC50 values were 4.21 0.46 μM amastigotes, respectively, indicating high selectivity clinically relevant stage. We found that leads a collapse membrane potential (ΔΨm) an increase in production reactive oxygen species, dose-dependent manner. Fluorescence microscopy cells labeled JC-1, marker energization, transmission electron confirmed severe alterations mitochondrion, including intense swelling modification its membranes. Other ultrastructural included (1) presence numerous lipid-storage bodies, (2) large autophagosomes containing part cytoplasm profiles, sometimes close association mitochondrion endoplasmic reticulum, (3) chromatin condensation plasma integrity. Taken together, our results indicate is potent inhibitor ofL. growth, acting through irreversible structure function, which lead cell death by necrosis, apoptosis and/or autophagy.