Author | Ribeiro, Grazielle Alves | |
Author | Cunha Junior, Edézio Ferreira | |
Author | Pinheiro, Roberta Olmo | |
Author | Silva, Silvia Amaral Gonçalves da | |
Author | Cavalheiro, Marilene Marcuzzo Canto | |
Author | Silva, Alcides José Monteiro da | |
Author | Costa, Paulo Roberto R. | |
Author | Daher Neto, Chaquip | |
Author | Melo, Rossana C. N. | |
Author | Amaral, Elmo Eduardo Almeida | |
Author | Santos, Eduardo Caio Torres | |
Access date | 2015-08-19T13:49:27Z | |
Available date | 2015-08-19T13:49:27Z | |
Document date | 2013 | pt_BR |
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. | pt_BR |
ISSN | 1460-2091 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/11525 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | restricted access | pt_BR |
Title | LQB-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in Leishmania amazonensis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1093/jac/dks498 | pt_BR |
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. | pt_BR |
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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas.Departamento de Parasitologia e Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Campus Macaé. Instituto de Química. Laboratório de Química Orgânica. Macaé, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Juiz de Fora. Laboratório de Biologia Celular. Juiz de Fora, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Chemotherapy | pt_BR |
Subject | Antiparasitic | pt_BR |
Subject | Quinones | pt_BR |
Subject | Leishmania amazonensis | pt_BR |
Subject | LQB-118 | pt_BR |
DeCS | Quinonas | pt_BR |
DeCS | Quimioterapia | pt_BR |
DeCS | Antiparasitários | pt_BR |
DeCS | Leishmania | pt_BR |