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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.)

Efficacy of tamoxifen and miltefosine combined therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis

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Author(s):
Trinconi, Cristiana T. [1] ; Reimao, Juliana Q. [1] ; Coelho, Adriano C. [1] ; Uliana, Silvia R. B. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Antimicrobial Chemotherapy; v. 71, n. 5, p. 1314-1322, MAY 2016.
Web of Science Citations: 14
Abstract

The objective of this study was to characterize in vitro interactions and evaluate the antileishmanial activity of tamoxifen and miltefosine combinations. Interactions between drugs were evaluated in vitro against Leishmania amazonensis promastigotes and intracellular amastigotes by a modified isobologram method. Four different drug ratios were used to calculate the FIC index (FICI) and the mean sum of FICI. Treatment of L. amazonensis-infected BALB/c mice was initiated 4 weeks post-infection. Mice were treated with the half-maximal effective dose (ED50) or half the ED50 of tamoxifen and miltefosine orally for 15 days. Efficacy was evaluated by lesion growth and parasite burden measured through luciferase detection at the end of treatment and 30 days later. Characterization of growth curves and stepwise increase in drug concentrations in vitro were used to measure survival and resistance selection of parasite populations submitted to combination treatment. No in vitro interactions between tamoxifen and miltefosine were found. In infected mice, the combination of tamoxifen and miltefosine at doses corresponding to half the ED50 was more effective than monotherapy with either tamoxifen or miltefosine. When the ED50 was employed, the efficacy of the combination was equivalent to miltefosine monotherapy. In vitro, tamoxifen was able to retard or suppress the growth of parasites treated with miltefosine. In vitro and in vivo studies revealed no interaction between tamoxifen and miltefosine. Tamoxifen was able to hinder the emergence of miltefosine resistance. (AU)

FAPESP's process: 11/18858-6 - TAMOXIFEN AS AN ANTI-LEISHMANIAL DRUG: ACTIVITY IN COMBINED THERAPEUTIC SCHEMES AND STUDY OF THE MECHANISM OF ACTION
Grantee:Cristiana de Melo Trinconi Tronco
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/14629-5 - Mechanisms of action and resistance to miltefosine in Leishmania spp.
Grantee:Adriano Cappellazzo Coelho
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/09080-2 - Evaluation of candidate drugs for the treatment of Leishmaniasis in Brazil
Grantee:Silvia Reni Bortolin Uliana
Support Opportunities: Regular Research Grants
FAPESP's process: 11/20484-7 - Tamoxifen in the treatment of leishmaniasis: evaluation of efficacy in combination therapy schemes and study of the antileishmanial mechanism of action
Grantee:Silvia Reni Bortolin Uliana
Support Opportunities: Regular Research Grants
FAPESP's process: 11/21970-2 - SELECTIVE ESTROGEN RECEPTOR MODULATORS AS DRUG CANDIDATES FOR VISCERAL LEISHMANIASIS: EVALUATION OF DRUG COMBINATIONS AND INVESTIGATION OF LEISHMANICIDAL MECHANISMS OF ACTION
Grantee:Juliana Quero Reimão Dalla Zanna
Support Opportunities: Scholarships in Brazil - Post-Doctoral