Tamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes

Abstract

Tamoxifen effectively kills several Leishmania species and its activity against the parasite is increased by a modulation of the host cell intravacuolar pH induced by the drug.

Effect of Human Urine on Cell Cycle and Infectivity of Leismania Species Promastigotes In Vitro

“…11 However, use of human urine as a supplementary material for Leishmania and Trypanosome culture have been reported in many studies. [12][13][14][15] There is no information on the effects of urine on the infectivity of Leishmania parasites. Therefore, the aim of this study was to investigate the effects of culture medium containing human urine on the infectivity of different species of Leishmania parasites ( L. tropica , L. infantum , L. donovani , and L. major ).…”

Determinação da sensibilidade de isolados de Leishmania a antimoniato de meglumina, anfotericina B e tamoxifeno.

“…8 In vitro effects of tamoxifen have also been established for fungal cells 9 and Leishmania parasites. 4 Having demonstrated the in vitro activity of tamoxifen against several species of Leishmania, we now show its effectiveness in vitro and in vivo against an L. braziliensis isolate obtained from a Brazilian patient with CL and on a L. chagasi reference strain.…”

“…3 We have previously shown that tamoxifen is active against several species of Leishmania in vitro. 4 Recently, we have also demonstrated that treatment of L. amazonensis-infected BALB/c mice with tamoxifen results in significant reductions in lesion and ulcer sizes, as well as in a sharp decrease in parasite burden. 5 In this work, we have focused on the investigation of tamoxifen efficacy in the treatment of leishmaniasis using two distinct rodent models to mimic CL and VL caused by L. braziliensis and L. chagasi, respectively.…”

“…The strains used were L. Drug cytotoxicity and activity against intracellular amastigotes were performed as described previously, 4 except that BALB/c bone marrow-derived macrophages were used. Assays with the reference drug meglumine antimoniate (kindly donated by Sanofi-Aventis) were performed in parallel as described previously.…”

“…braziliensis and L. chagasi promastigotes differentiated from amastigotes recovered from treated animals were used to test drug sensitivity by determination of tamoxifen IC 50 through cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as previously described. 4 Statistical analysis was performed using one-way ANOVA followed by Dunnett's post hoc test (GraphPad Prism, CA, USA). A P value of ,0.05 was considered statistically significant.…”