PMID- 25340550
OWN - NLM
STAT- MEDLINE
DCOM- 20150625
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 10
DP  - 2014
TI  - Pterocarpanquinone LQB-118 induces apoptosis in Leishmania (Viannia) braziliensis 
      and controls lesions in infected hamsters.
PG  - e109672
LID - 10.1371/journal.pone.0109672 [doi]
LID - e109672
AB  - Previous results demonstrate that the hybrid synthetic pterocarpanquinone LQB-118 
      presents antileishmanial activity against Leishmania amazonensis in a mouse 
      model. The aim of the present study was to use a hamster model to investigate 
      whether LQB-118 presents antileishmanial activity against Leishmania (Viannia) 
      braziliensis, which is the major Leishmania species related to American 
      tegumentary leishmaniasis. The in vitro antileishmanial activity of LQB-118 on L. 
      braziliensis was tested on the promastigote and intracellular amastigote forms. 
      The cell death induced by LQB-118 in the L. braziliensis promastigotes was 
      analyzed using an annexin V-FITC/PI kit, the oxidative stress was evaluated by 
      2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and the ATP content by 
      luminescence. In situ labeling of DNA fragments by terminal deoxyribonucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate 
      apoptosis in the intracellular amastigotes. L. braziliensis-infected hamsters 
      were treated from the seventh day of infection with LQB-118 administered 
      intralesionally (26 microg/kg/day, three times a week) or orally (4,3 mg/kg/day, five 
      times a week) for eight weeks. LQB-118 was active against the L. braziliensis 
      promastigotes and intracellular amastigotes, producing IC50 (50% inhibitory 
      concentration) values of 3,4+/-0,1 and 7,5+/-0,8 microM, respectively. LQB-118 induced 
      promastigote phosphatidylserine externalization accompanied by increased reactive 
      oxygen species production and ATP depletion. Intracellular amastigote DNA 
      fragmentation was also observed, without affecting the viability of macrophages. 
      The treatment of L. braziliensis-infected hamsters with LQB-118, either orally or 
      intralesionally, was effective in the control of lesion size, parasite load and 
      increase intradermal reaction to parasite antigen. Taken together, these results 
      show that the antileishmanial effect of LQB-118 extends to L. braziliensis in the 
      hamster model, involves the induction of parasite apoptosis and shows promising 
      therapeutic option by oral or local routes in leishmaniasis.
FAU - Costa, Luciana
AU  - Costa L
AD  - Laboratorio de Imunofarmacologia Parasitaria, Departamento de Microbiologia, 
      Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
FAU - Pinheiro, Roberta O
AU  - Pinheiro RO
AD  - Laboratorio de Hanseniase, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 
      Brazil.
FAU - Dutra, Patricia M L
AU  - Dutra PM
AD  - Laboratorio de Bioquimica de Protozoarios e Imunofisiologia do Exercicio, 
      Departamento de Microbiologia, Imunologia e Parasitologia, Universidade do Estado 
      do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Santos, Rosiane F
AU  - Santos RF
AD  - Laboratorio de Imunofarmacologia Parasitaria, Departamento de Microbiologia, 
      Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
FAU - Cunha-Junior, Edezio F
AU  - Cunha-Junior EF
AD  - Laboratorio de Bioquimica de Tripanosomatideos, Instituto Oswaldo Cruz, FIOCRUZ, 
      Rio de Janeiro, Brazil.
FAU - Torres-Santos, Eduardo C
AU  - Torres-Santos EC
AD  - Laboratorio de Bioquimica de Tripanosomatideos, Instituto Oswaldo Cruz, FIOCRUZ, 
      Rio de Janeiro, Brazil.
FAU - da Silva, Alcides J M
AU  - da Silva AJ
AD  - Laboratorio de Catalise Organica, Nucleo de Pesquisas de Produtos Naturais, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Costa, Paulo R R
AU  - Costa PR
AD  - Laboratorio de Quimica Bioorganica - Nucleo de Pesquisas de Produtos Naturais, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Da-Silva, Silvia A G
AU  - Da-Silva SA
AD  - Laboratorio de Imunofarmacologia Parasitaria, Departamento de Microbiologia, 
      Imunologia e Parasitologia, Universidade do Estado do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141023
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antiprotozoal Agents)
RN  - 0 (LQB 118)
RN  - 0 (Naphthoquinones)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Pterocarpans)
SB  - IM
MH  - Animals
MH  - Antiprotozoal Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cricetinae
MH  - Female
MH  - Leishmania braziliensis/*drug effects
MH  - Leishmaniasis, Cutaneous/*parasitology/pathology
MH  - Macrophages/drug effects/parasitology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mesocricetus
MH  - Naphthoquinones/*pharmacology
MH  - Phosphatidylserines/metabolism
MH  - Pterocarpans/*pharmacology
PMC - PMC4207686
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/24 06:00
MHDA- 2015/06/26 06:00
PMCR- 2014/10/23
CRDT- 2014/10/24 06:00
PHST- 2014/05/30 00:00 [received]
PHST- 2014/09/03 00:00 [accepted]
PHST- 2014/10/24 06:00 [entrez]
PHST- 2014/10/24 06:00 [pubmed]
PHST- 2015/06/26 06:00 [medline]
PHST- 2014/10/23 00:00 [pmc-release]
AID - PONE-D-14-23153 [pii]
AID - 10.1371/journal.pone.0109672 [doi]
PST - epublish
SO  - PLoS One. 2014 Oct 23;9(10):e109672. doi: 10.1371/journal.pone.0109672. 
      eCollection 2014.