Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide
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2014
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Background: Leishmania amazonensis infection results in diverse clinical manifestations: cutaneous, mucocutaneous
or visceral leishmaniasis. The arsenal of drugs available for treating Leishmania infections is limited. Therefore, new,
effective, and less toxic leishmaniasis treatments are still needed. We verified cell death in amastigote forms of
Leishmania amazonensis induced by the sesquiterpene lactone parthenolide.
Results: The tested compound was able to concentration-dependently affect axenic and intracellular amastigotes,
with IC50 values of 1.3 μM and 2.9 μM, respectively after 72 h incubation. No genotoxic effects were observed in a
micronucleus test in mice. Parthenolide induced morphological and ultrastructural changes in axenic amastigotes,
including a loss of membrane integrity, swelling of the mitochondrion, cytoplasmic vacuoles, and intense exocytic
activity in the region of the flagellar pocket. These results led us to investigate the occurrence of autophagic vacuoles
with monodansylcadaverine and the integrity of the plasma membrane and mitochondrial membrane potential using
flow cytometry. In all of the tests, parthenolide had positive results.
Conclusions: Our results indicate that the antileishmanial action of parthenolide is associated with autophagic vacuole
appearance, a reduction of fluidity, a loss of membrane integrity, and mitochondrial dysfunction. Considering the limited
repertoire of existing antileishmanial compounds, the products derived from medicinal plants has been one the greatest
advances to help develop new chemotherapeutic approaches.
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Leishmania amazonensis, Amastigotes, Parthenolide, Cell death, Autophagy
Citação
TIUMAN, Tatiana Shioji; UEDA-NAKAMURA, Tânia; ALONSO, Antonio; NAKAMURA, Celso Vataru. Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide. BMC Microbiology, London, v. 14, n. 152, p. 1-12, 2014.