title: Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide.
abstract: 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.
authors.forename: Tatiana Shioji
authors.initials: TS
authors.lastname: Tiuman
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Antonio
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av, Colombo 5790, 87020-900 Maringá, Paraná, Brazil. cvnakamura@uem.br.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000981:Antiprotozoal Agents; D012717:Sesquiterpenes; C002669:parthenolide