Abstract
BackgroundLeishmania 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.ResultsThe 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.ConclusionsOur 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.
Highlights
Leishmania amazonensis infection results in diverse clinical manifestations: cutaneous, mucocutaneous or visceral leishmaniasis
We evaluated the activity of parthenolide against L. amazonensis axenic amastigotes and demonstrated a possible mechanism of action of this compound in this life stage of the parasite
A concentration of 1.0 or 0.5 μM of the reference drug amphotericin B inhibited more than 93% of L. amazonensis amastigote cell growth
Summary
Leishmania amazonensis infection results in diverse clinical manifestations: cutaneous, mucocutaneous or visceral leishmaniasis. The arsenal of drugs available for treating Leishmania infections is limited. New, effective, and less toxic leishmaniasis treatments are still needed. Leishmaniasis is associated with high morbidity but low mortality. It is a poverty-related disease and has become a serious impediment to socioeconomic development. The true burden of this illness remains unclear because the notification of the disease is compulsory in only 32 of the 88 affected countries, and most of the affected people live in remote areas. An estimated 1.5 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis occur annually, with approximately 12 million people currently infected [1]. Cases of Leishmania and human immunodeficiency virus co-infection are becoming more frequent [2,3]
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