| Full text | |
| 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 |