Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice.
Leishmaniasis is one of the most serious worldwide diseases caused by protozoan parasites of the Leishmania genus, affecting millions of people around the world. All currently available treatments present severe toxic side effects, require long-term compliance, cause serious side effects and are uncomfortable for patients. Leishmania amazonensis, a species endemic to Brazil, causes severe localised or diffuse skin lesions in humans. Owing to the unsatisfactory nature of the currently available chemotherapies, new approaches have been assessed for improved therapeutic intervention strategies against leishmaniasis. Miltefosine is an alkylphospholipid analogue that exhibits potent activity against the different clinical manifestations of leishmaniasis. Thus, the aim of this study was to investigate the long-term efficacy of miltefosine in BALB/c mice infected with L. amazonensis owing to the lack of a profound study demonstrating its dose-dependent and long-term effects. It was observed that animals treated with 20-50 mg/kg/day of miltefosine exhibited a significant dose-dependent reduction in lesion size; furthermore, in mice receiving higher doses, lesions disappeared after the end of treatment. To confirm a possible parasitological cure, mice up to 250 days after the end of treatment were analysed. No lesions or presence of parasite DNA were found in mice treated with 30, 40 and 50 mg/kg/day of miltefosine. In summary, these results show that miltefosine may be used to treat cutaneous leishmaniasis caused by L. amazonensis, alone or as combination therapy.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas 373, CCS, Ilha do Fundão, Rio de Janeiro 21941-902, Brazil.
Joseane Lima Prado
JL
Godinho
Cíntia
C
Simas-Rodrigues
Rosane
R
Silva
Turán Peter
TP
Ürmenyi
Wanderley
W
de Souza
Juliany Cola Fernandes
JC
Rodrigues
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001399:Azure Stains / Q000737:chemistry; D016054:DNA, Protozoan / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007891:Leishmania / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology; D059208:Parasite Load; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014456:Ulcer / Q000188:drug therapy / Q000469:parasitology
D000981:Antiprotozoal Agents; D001399:Azure Stains; D016054:DNA, Protozoan; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate