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 (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.
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 (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.
Authors: Cristiana T Trinconi; Juliana Q Reimão; Jenicer K U Yokoyama-Yasunaka; Danilo C Miguel; Silvia R B Uliana Journal: Antimicrob Agents Chemother Date: 2014-02-18 Impact factor: 5.191
Authors: Isabella Aparecida Salerno Pimentel; Carolina de Siqueira Paladi; Simone Katz; Wagner Alves de Souza Júdice; Rodrigo L O R Cunha; Clara Lúcia Barbiéri Journal: PLoS One Date: 2012-11-07 Impact factor: 3.240
Authors: Juliana Q Reimão; Jordana C Oliveira; Cristiana T Trinconi; Paulo C Cotrim; Adriano C Coelho; Silvia R B Uliana Journal: PLoS Negl Trop Dis Date: 2015-02-13
Authors: Elizabeth R Sharlow; David Close; Tongying Shun; Stephanie Leimgruber; Robyn Reed; Gabriela Mustata; Peter Wipf; Jacob Johnson; Michael O'Neil; Max Grögl; Alan J Magill; John S Lazo Journal: PLoS Negl Trop Dis Date: 2009-11-03