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Aurea Echevarria - One of the best experts on this subject based on the ideXlab platform.

Celso Vataru Nakamura - One of the best experts on this subject based on the ideXlab platform.

  • cell death in amastigote forms of Leishmania amazonensis induced by parthenolide
    BMC Microbiology, 2014
    Co-Authors: Tatiana Shioji Tiuman, Tânia Uedanakamura, Antonio Alonso, Celso Vataru Nakamura
    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.

  • mitochondria superoxide anion production contributes to geranylgeraniol induced death in Leishmania amazonensis
    Evidence-based Complementary and Alternative Medicine, 2012
    Co-Authors: Milene Valeria Lopes, Tânia Uedanakamura, Vânia Cristina Desoti, Angelo De Oliveira Caleare, Sueli De Oliveira Silva, Celso Vataru Nakamura
    Abstract:

    Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds of Bixa orellana, against Leishmania amazonensis. Geranylgeraniol was identified through 1H and 13C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC50 of and  μg/mL, respectively. This compound was also more toxic to parasites than to macrophages and did not cause lysis in human blood cells. Morphological and ultrastructural changes induced by geranylgeraniol were observed in the protozoan by electronic microscopy and included mainly mitochondria alterations and an abnormal chromatin condensation in the nucleus. These alterations were confirmed by Rh 123 and TUNEL assays. Additionally, geranylgeraniol induces an increase in superoxide anion production. Collectively, our in vitro studies indicate geranylgeraniol as a selective antiLeishmanial that appears to be mediated by apoptosis-like cell death.

  • Effects of (−) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis
    Phytomedicine, 2012
    Co-Authors: M A Brenzan, Celso Vataru Nakamura, Adriana Oliveira Dos Santos, B P Dias Filho, T Ueda-nakamura, M C M Young, A G Côrrea, J Alvim Júnior, J A Morgado-díaz, D A G Cortez
    Abstract:

    Abstract We have previously demonstrated antiLeishmanial activity on Leishmania amazonensis of the natural (1–2), synthetic (7) and derivatives of coumarin (−) mammea A/BB (3–6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antiLeishmanial with LD50 of 0.9 μM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite.

  • effect of brazilian copaiba oils on Leishmania amazonensis
    Journal of Ethnopharmacology, 2008
    Co-Authors: Adriana Oliveira Dos Santos, Tânia Uedanakamura, Celso Vataru Nakamura, Benedito Prado Dias Filho, Valdir Florencio Da Veiga, Angelo C Pinto
    Abstract:

    Abstract Ethnopharmacological relevance Copaiba oil has been used in folk medicine since the 19th century. The use of copaiba oils to treat Leishmaniasis is cited in several ethnopharmacological studies. Nevertheless, the potential antiLeishmania of copaiba oils had not been studied. Aim of the study Eight different kinds of Brazilian copaiba oils were screened for antiLeishmanial activity. Materials and methods The antiproliferative effect of copaiba oil on promastigote and amastigote axenic were determined. To determine the survival index peritoneal macrophage were infected with promastigotes of Leishmania amazonensis and treated with copaiba oil. The cytotoxic effect of copaiba oil was assessed on macrophage strain J774G8 by assay of sulforhodamine B. Results Copaiba oils showed variable levels of activity against promastigote forms with IC50 values in the range between 5 and 22 μg/mL. The most active oil was that from Copaifera reticulata (collected in Para State, Brazil) with IC50 values of 5, 15, and 20 μg/mL for promastigote, axenic amastigote and intracellular amastigote forms, respectively. Amphotericin B showed IC50 of 0.058 and 0.231 μg/mL against promastigote and amastigote forms, respectively. Cytotoxicity assay showed that this copaiba oil obtained from Copaifera reticulata showed low cytotoxicity against J774G8 macrophages. Conclusion Copaiba oils showed significant activity against the parasite Leishmania amazonensis.

Leonor L. Leon - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Oral Treatment with Pyrazole Carbohydrazide Derivatives against Murine Infection by Leishmania amazonensis
    American Journal of Tropical Medicine and Hygiene, 2009
    Co-Authors: Karen S. Charret, Leonor L. Leon, Raquel Fonseca Rodrigues, Marilene M. Canto-cavalheiro, Alice M. R. Bernardino, Adriana O. Gomes, Adriana V. Carvalho, Veronica F. Amaral
    Abstract:

    Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO 2 and X = NO 2 /Y = Cl were independently investigated in the CBA mouse model of cutaneous Leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohy- drazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspar- tate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against Leishmaniasis. 1 It is caused by protozoans of the genus Leishmania and the bite of phleboto- mine sand flies. In Brazil, Leishmania amazonensis is responsi- ble for most cases reported, which include cutaneous, mucosal, diffuse cutaneous, and visceral Leishmaniasis, and is considered a species of epidemiologic importance. 2-4

  • AntiLeishmanial Activity of 1,3,4-Thiadiazolium-2-Aminide in Mice Infected with Leishmania amazonensis
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: Raquel Fonseca Rodrigues, Leonor L. Leon, Karen S. Charret, Edson Fernandes Silva, Aurea Echevarria, Veronica F. Amaral, Marilene M. Canto-cavalheiro
    Abstract:

    The efficacy of two mesoionic derivatives (MI-H-H and MI-4-OCH3) was evaluated in CBA/J mice infected with Leishmania amazonensis. Treatment with these compounds demonstrated that the MI-4-OCH3 derivative and the reference drug meglumine antimoniate (Glucantime) presented significant activity relative to an untreated control. No apparent hepatic or renal toxicity due to these mesoionic compounds was found.

  • Nitric oxide synthase (NOS) characterization in Leishmania amazonensis axenic amastigotes.
    Archives of Medical Research, 2006
    Co-Authors: Marcelo Genestra, Léa Cysne-finkelstein, Damiana Guedes-silva, Wilson Jacinto Silva De Souza, Rômulo José Soares-bezerra, Fabiane Pereira Monteiro, Leonor L. Leon
    Abstract:

    Background Although Leishmania virulence may be modulated by environmental and genetic factors of their mammalian hosts and sand fly vectors, molecular determinants of Leishmania sp. are the key elements. This work evidences that Leishmania amazonensis axenic amastigotes produce comparatively more NO than infective promastigotes. Methods A soluble NOS was purified from L. amazonensis axenic amastigotes by affinity chromatography (2′,5′-ADP-agarose), and on SDS-PAGE the enzyme migrates as a single protein band. Results The presence of a constitutive NOS was detected through immunofluorescence using antibody against neuronal NOS (nNOS) and in NADPH consumption assays. Conclusions The present data show that NOS is prominent in axenic amastigote preparations, suggesting an association with the infectivity and/or an escaping mechanism of the parasite. The relationship between the NO-generating systems in the parasite and in their host cell warrants further investigation.

  • Cyclic 3'-5' guanosine monophosphate-dependent activity in Leishmania amazonensis
    Memorias Do Instituto Oswaldo Cruz, 2003
    Co-Authors: Lf Géigel, Leonor L. Leon
    Abstract:

    Although there are some data concerning the nitric oxide and the cyclic 3'-5'guanosine monophosphate (cGMP) signaling pathway in trypanosomatids, there is no report about the cGMP-dependent enzymatic activity identification. In this sense, a cGMP dependent activity was detected on soluble fraction from Leishmania amazonensis promastigotes with a high metacyclic level. This information is valuable in order to explore the metabolic pathway of G kinase protein in this parasite.

  • Efficacy of a diarylheptanoid derivative against Leishmania amazonensis
    Memorias Do Instituto Oswaldo Cruz, 2003
    Co-Authors: Luciana Vignólio Alves, Rosane Maria Temporal, Léa Cysne-finkelstein, Leonor L. Leon
    Abstract:

    The activity of several diarylheptanoid derivatives (curcuminoids) was previously evaluated against Leishmania amazonensis promastigotes and among them the most active compound was the [1-(4-methoxy-phenyl)-7-(3,4-methoxy-4-hydroxy-phenyl)-1,6-heptadien-3, 5-dione]. This derivative was chosen to be assayed in vivo in a treatment trial. For these experiments, the curcuminoid compound was used in a concentration equivalent to the IC50/24 h, obtained from the previous study. Balb/c mice were inoculated subcutaneously in the footpad with L. amazonensis infective promastigotes and 4 weeks after the inoculation, the animals were treated with different schemes, varying from 1 to 3 doses. In all the experiments, Pentamidine Isethionate was used as reference drug under the same experimental conditions. The results showed that one dose was not enough to heal the lesion, however, with 2 and 3 doses the efficiency of the assayed compound was clear. On the other hand, treatment with Pentamidine Isethionate using the three different schemes was not satisfactory when compared to the curcuminoid derivative.

Edson F Da Silva - One of the best experts on this subject based on the ideXlab platform.

Herbert Leonel De Matos Guedes - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of Sv129 Mice as a Susceptible Model to Leishmania amazonensis
    Frontiers in Medicine, 2019
    Co-Authors: Julio Souza Dos-santos, Luan Firmino-cruz, Tadeu Diniz Ramos, Alessandra Marcia Da Fonseca-martins, Diogo Oliveira-maciel, Juliana Valente Rodrigues De-medeiros, Suzana Passos Chaves, Daniel Cláudio De Oliveira Gomes, Herbert Leonel De Matos Guedes
    Abstract:

    Leishmaniasis is a complex of neglected diseases caused by parasites of the genus Leishmania, such as Leishmania (Leishmania) amazonensis, the ethiologic agent of diffuse cutaneous Leishmaniasis in Brazil. In this work, we investigated a new experimental model of infection for L. amazonensis: the Sv129 mouse. First, we subcutaneously infected Sv129 mice with 2x105 or 2x106 L. amazonensis parasites of the Josefa strain. A progressive lesion developed for both inoculation doses, showing that Sv129 mice are susceptible, independent of parasite dose. We next investigated the mechanisms associated with the pathogenesis of infection. We did not observe an increase of frequency of interferon-gamma (IFN- γ)-producing CD4+ and CD8+ T cells, a phenotype similar to that seen in BALB/c mice. There was an increased of frequency and number of IL-17-producing γδ (gamma-delta) T cells in infected Sv129 mice compared to naive SV129 and an increased frequency of this population compared to infected BALB/c mice. In addition, Sv129 mice presented high levels of both IgG1 and IgG2a, suggesting a mixed Th1 and Th2 response with a skew towards IgG1 production based on IgG1/IgG2a ratio. Susceptibility of the Sv129 mice was further confirmed with the use of another strain of L. amazonensis, LTB0016. In this work, we characterized the Sv129 mice as a new model of susceptibility to Leishmania amazonensis infection, during infection there was controlled IFN-γ production by CD4+ or CD8+ T cells and induced IL-17 production by γδ T cells.

  • the comparative genomics and phylogenomics of Leishmania amazonensis parasite
    Evolutionary Bioinformatics, 2014
    Co-Authors: Diogo A Tschoeke, Gisele L Nunes, Rodrigo Jardim, Joana Lima, Aline Sr Dumaresq, Monete Rajao Gomes, Leandro De Mattos Pereira, Daniel R Loureiro, Patricia Hermes Stoco, Herbert Leonel De Matos Guedes
    Abstract:

    Leishmaniasis is an infectious disease caused by Leishmania species. Leishmania amazonensis is a New World Leishmania species belonging to the Mexicana complex, which is able to cause all types of Leishmaniasis infections. The L. amazonensis reference strain MHOM/BR/1973/M2269 was sequenced identifying 8,802 codifying sequences (CDS), most of them of hypothetical function. Comparative analysis using six Leishmania species showed a core set of 7,016 orthologs. L. amazonensis and Leishmania mexicana share the largest number of distinct orthologs, while Leishmania braziliensis presented the largest number of inparalogs. Additionally, phylogenomic analysis confirmed the taxonomic position for L. amazonensis within the “Mexicana complex”, reinforcing understanding of the split of New and Old World Leishmania. Potential non-homologous isofunctional enzymes (NISE) were identified between L. amazonensis and Homo sapiens that could provide new drug targets for development.

  • intranasal vaccination with extracellular serine proteases of Leishmania amazonensis confers protective immunity to balb c mice against infection
    Parasites & Vectors, 2014
    Co-Authors: Herbert Leonel De Matos Guedes, Suzana Passos Chaves, Beatriz Lilian Da Silva Costa, Daniel Claudio Oliveira Gomes, Joshua D Nosanchuk, Salvatore Giovanni De Simone, Bartira Rossibergmann
    Abstract:

    Background: Previously, we demonstrated that unlike subcutaneous or intramuscular vaccination, intranasal vaccination of BALB/c mice with whole Leishmania amazonensis antigens leads to protection against cutaneous Leishmaniasis. Here, the role of parasite serine proteases in the protective immunity was investigated. Findings: Serine Proteases were partially purified from both soluble (LaSP-Sol) and extracellular (LaSP-Ex) Leishmania amazonensis promastigote extracts by aprotinin-agarose chromatography. BALB/c mice were intranasally immunized with LaSP-Sol and LaSP-Ex prior to infection with L. amazonensis. LaSP-Ex but not LaSP-Sol vaccination led to significantly smaller lesions and parasite burdens as compared with non-vaccinated controls. Protection was accompanied by systemic Th1 polarization with increased IFN-γ and decreased IL-4 and IL-10 splenic production. Likewise, increased production of IFN-γ, IL-12 and IL-4 concomitant with decreased TGF-β and TNF-α was locally observed in the infected footpad. Conclusion: This study indicates that extracellular serine proteases of L. amazonensis are strong candidates for a more defined intranasal vaccine against cutaneous Leishmaniasis.

  • Intranasal vaccination with extracellular serine proteases of Leishmania amazonensis confers protective immunity to BALB/c mice against infection
    Parasites & Vectors, 2014
    Co-Authors: Herbert Leonel De Matos Guedes, Suzana Passos Chaves, Daniel Cláudio De Oliveira Gomes, Beatriz Lilian Da Silva Costa, Joshua D Nosanchuk, Salvatore Giovanni De Simone, Bartira Rossi-bergmann
    Abstract:

    Background: Previously, we demonstrated that unlike subcutaneous or intramuscular vaccination, intranasal vaccination of BALB/c mice with whole Leishmania amazonensis antigens leads to protection against cutaneous Leishmaniasis. Here, the role of parasite serine proteases in the protective immunity was investigated. Findings: Serine Proteases were partially purified from both soluble (LaSP-Sol) and extracellular (LaSP-Ex) Leishmania amazonensis promastigote extracts by aprotinin-agarose chromatography. BALB/c mice were intranasally immunized with LaSP-Sol and LaSP-Ex prior to infection with L. amazonensis. LaSP-Ex but not LaSP-Sol vaccination led to significantly smaller lesions and parasite burdens as compared with non-vaccinated controls. Protection was accompanied by systemic Th1 polarization with increased IFN-γ and decreased IL-4 and IL-10 splenic production. Likewise, increased production of IFN-γ, IL-12 and IL-4 concomitant with decreased TGF-β and TNF-α was locally observed in the infected footpad. Conclusion: This study indicates that extracellular serine proteases of L. amazonensis are strong candidates for a more defined intranasal vaccine against cutaneous Leishmaniasis.