Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections.
OBJECTIVE
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 (IC(50)) of 1.9 +/- 0.2 and 2.4 +/- 0.3 microM, 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.
Miguel
Danilo C
DC
Department of Parasitology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil.
Zauli-Nascimento
Rogéria C
RC
Yokoyama-Yasunaka
Jenicer K U
JK
Katz
Simone
S
Barbiéri
Clara L
CL
Uliana
Silvia R B
SR
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006224:Cricetinae; D005260:Female; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D012867:Skin / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D013629:Tamoxifen