Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11525
Title: LQB-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in Leishmania amazonensis
Authors: Ribeiro, Grazielle Alves
Cunha Junior, Edézio Ferreira
Pinheiro, Roberta Olmo
Silva, Silvia Amaral Gonçalves da
Cavalheiro, Marilene Marcuzzo Canto
Silva, Alcides José Monteiro da
Costa, Paulo Roberto R.
Daher Neto, Chaquip
Melo, Rossana C. N.
Amaral, Elmo Eduardo Almeida
Santos, Eduardo Caio Torres
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil / Universidade Federal de Juiz de Fora. Laboratório de Biologia Celular. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas.Departamento de Parasitologia e Microbiologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Campus Macaé. Instituto de Química. Laboratório de Química Orgânica. Macaé, RJ, Brasil.
Universidade Federal de Juiz de Fora. Laboratório de Biologia Celular. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Abstract: Objectives: The pterocarpanquinone LQB-118, previously demonstrated to be effective in vivo via oral delivery, was investigated for its mechanism in selective parasite killing. Methods: Oxidative stress in Leishmania amazonensis was analysed by evaluating reactive oxygen species (ROS) production (2′,7′-dichlorodihydrofluorescein diacetate) and the loss of mitochondrial membrane potential (DCm) using rhodamine, JC-1 and MitoCapture. Ultrastructural analysis was performed using transmission electron microscopy (TEM). DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferasemediated dUTP nick-end labelling (TUNEL). Results: Treatment with LQB-118 induced ROS production in the promastigotes of L. amazonensis in a concentration- dependent manner for the first 4 h and was sustained for 24 h. TEM analysis revealed several alterations typical of apoptosis. Promastigotes presented a reduction of DCm after 24 h of incubation with 2.5 mM (18.7%), 5 mM (63.7%) or 10 mM (70.7%) LQB-118. A sub-G0/G1 cell cycle phenotype was observed in 21%– 83% of the promastigotes incubated with 1.25–10 mM LQB-118. Concentration-dependent DNA fragmentation was observed in promastigotes treated with 2.5–10 mM LQB-118, and selective DNA fragmentation was observed in intracellular amastigotes after 72 h with 2.5 mM treatment. Conclusions: Our results suggest that LQB-118 selectively induces ROS-triggered and mitochondria-dependent apoptosis in this parasite.
Keywords: Chemotherapy
Antiparasitic
Quinones
Leishmania amazonensis
LQB-118
DeCS: Quinonas
Quimioterapia
Antiparasitários
Leishmania
Issue Date: 2013
Publisher: Oxford University Press
Citation: RIBEIRO, Grazielle Alves; et al. LQB-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in Leishmania amazonensis. J Antimicrob Chemother. v.68, n.4, p.789–799, 2013.
DOI: 10.1093/jac/dks498
ISSN: 1460-2091
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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