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JAC Advance Access originally published online on December 17, 2008
Journal of Antimicrobial Chemotherapy 2009 63(2):365-368; doi:10.1093/jac/dkn509
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections

Danilo C. Miguel1,{dagger}, Rogéria C. Zauli-Nascimento1,{dagger}, Jenicer K. U. Yokoyama-Yasunaka1, Simone Katz2, Clara L. Barbiéri2 and Silvia R. B. Uliana1,*

1 Department of Parasitology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil 2 Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil

Received 29 August 2008; returned 3 November 2008; revised 6 November 2008; accepted 23 November 2008

* Corresponding author. Tel: +55-11-30917334; Fax: +55-11-30917417; E-mail: srbulian{at}icb.usp.br

Objectives: The aim of this study was to evaluate the efficacy of tamoxifen in vivo in experimental models of cutaneous (CL) and visceral leishmaniasis (VL) caused by Leishmania braziliensis and Leishmania chagasi, respectively.

Methods: Drug activity was assessed against intracellular amastigotes by treating infected macrophage cultures and evaluating the number of infected cells. In vivo efficacy of tamoxifen was tested in L. braziliensis-infected BALB/c mice and in L. chagasi-infected hamsters. Treatment with 20 mg/kg/day tamoxifen was administered for 15 days by the intraperitoneal route. Efficacy was evaluated through measurements of lesion size, parasite burden at the lesion site or liver and spleen and survival rate.

Results: Tamoxifen killed L. braziliensis and L. chagasi intracellular amastigotes with 50% inhibitory concentrations (IC50) of 1.9 ± 0.2 and 2.4 ± 0.3 µM, respectively. Treatment of L. braziliensis-infected mice with tamoxifen resulted in significant reductions in lesion size and 99% decrease in parasite burden, compared with mock-treated controls. L. chagasi-infected hamsters treated with tamoxifen showed significant reductions in liver parasite load expressed as Leishman–Donovan units and 95% to 98% reduction in spleen parasite burden. All animals treated with tamoxifen survived while 100% of the mock-treated animals had died by 11 weeks after the interruption of treatment.

Conclusions: Tamoxifen is effective in the treatment of CL and VL in rodent models.

Keywords: chemotherapy , cutaneous leishmaniasis , visceral leishmaniasis , selective oestrogen receptor modulator , SERM

{dagger} Both authors contributed equally to this work.


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