Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide

• Published in: BMC microbiology 2014-06, Vol.14 (1), p.152-152, Article 152
• Main Authors: Tiuman, Tatiana Shioji, Ueda-Nakamura, Tânia, Alonso, Antonio, Nakamura, Celso Vataru
• Format: Article
• Language: English
• Subjects: Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Care and treatment; Cell Death; Cell Membrane - drug effects; Cell Membrane - ultrastructure; Complications and side effects; Development and progression; Female; Genetic aspects; Genetic diversity; Health aspects; Inhibitory Concentration 50; Leishmania amazonensis; Leishmania mexicana - cytology; Leishmania mexicana - drug effects; Leishmania mexicana - ultrastructure; Leishmaniasis; Male; Medicine, Botanic; Medicine, Herbal; Mice; Mice, Inbred BALB C; Microscopy; Microscopy, Electron; Mortality; Organelles - drug effects; Organelles - ultrastructure; Parasites; Parasitic diseases; Patient outcomes; Risk factors; Sesquiterpenes - pharmacology; Sesquiterpenes - toxicity; Studies; Toxicity
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/1471-2180-14-152

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. 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. 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.