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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Leishmanicidal and Immunomodulatory Activities of the Palladacycle Complex DPPE 1.1, a Potential Candidate for Treatment of Cutaneous Leishmaniasis

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Author(s):
dos Santos, Isabela B. [1] ; da Silva, Danielle A. M. [1] ; Paz, Fabiana A. C. R. [1] ; Garcia, Daniel M. [2] ; Carmona, Adriana K. [3] ; Teixeira, Daniela [1] ; Longo-Maugeri, Ieda M. [1] ; Katz, Simone [1] ; Barbieri, Clara L. [1]
Total Authors: 9
Affiliation:
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Farmacol, Escola Paulista Med, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Biofis, Escola Paulista Med, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: FRONTIERS IN MICROBIOLOGY; v. 9, JUL 3 2018.
Web of Science Citations: 3
Abstract

The present study focused on the activity of the palladacycle complex DPPE 1.1 on Leishmania (Leishmania) amazonensis, Promastigotes of L. (L.) amazonensis were destroyed in vitro by nanomolar concentrations of DPPE 1.1, whereas intracellular amastigotes were killed at drug concentrations fivefold less toxic than those harmful to macrophages. L. (L.) amazonensis-infected BALB/c mice were treated by intralesional injection of DPPE 1.1. Animals treated with 3.5 and 7.0 mg/kg of DPPE 1.1 showed a significant decrease of foot lesion sizes and a parasite load reduction of 93 and 99%, respectively, when compared to untreated controls. Furthermore, DPPE 1.1 was non-toxic to treated animals. The cathepsin B activity of L. (L.) amazonensis amastigotes was inhibited by DPPE 1.1 as demonstrated spectrofluorometrically by use of a specific fluorogenic substrate. Analysis of T-cells populations in mice treated wrth DPPE 1.1 and untreated controls was performed by fluorescence-activated cell sorter (FACS), IFN-gamma was measured in supernatants of lymphocytes from popliteal and inguinal lymph nodes isolated from treated and untreated mice and stimulated with L. (L.) amazonensis amastigotes extract and active TGF-beta was evaluated in supernatants of foot lesions; both dosages were earned out by means of a double-sandwich ELISA assay. A significant increase of TCD4(+) and TCD8(+) lymphocytes and IFN-gamma secretion was displayed in mice treated with DPPE 1.1 compared to untreated animals, whereas a significant reduction of active TGF-beta was observed in treated mice. These findings open perspectives for further investment in DPPE 1.1 as an alternative option for the chemotherapy of cutaneous leishmaniasis. (AU)

FAPESP's process: 14/06935-4 - Effect of the treatment with the paladacycle complex DPPE 1.2 associated to the recombinant cysteine proteinase rLdccys1 on Leishmania (Leishmania) amazonensis infection in a murine model
Grantee:Danielle Aparecida Marino da Silva
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 13/02133-8 - Leishmanicidal activity of palladacycle complexes: in vitro and in vivo inhibitory effect of DPPE 1.1 on Leishmania (Leishmania) amazonensis and evaluation of immune responses in infected mice treated with DPPE 1.2
Grantee:Clara Lúcia Barbiéri Mestriner
Support Opportunities: Regular Research Grants