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Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms

Bertão, Humberto Gonçalves ; da Silva, Renata Alexandre Ramos ; Padilha, Rafael José R. ; de Azevedo Albuquerque, Mônica Camelo Pessôa ; Rádis-Baptista, Gandhi

Parasitology research (1987), 2012-06, Vol.110 (6), p.2465-2473 [Revista revisada por pares]

Berlin/Heidelberg: Springer-Verlag

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Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms
Autor: Bertão, Humberto Gonçalves ; da Silva, Renata Alexandre Ramos ; Padilha, Rafael José R. ; de Azevedo Albuquerque, Mônica Camelo Pessôa ; Rádis-Baptista, Gandhi
Materias: Animals ; Anthelmintics - pharmacology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Dose-Response Relationship, Drug ; Fundamental and applied biological sciences. Psychology ; General aspects ; General aspects and techniques. Study of several systematic groups. Models ; Health aspects ; Immunology ; Invertebrates ; Leishmania ; Medical Microbiology ; Membrane proteins ; Microbiology ; Microscopy, Electron, Scanning ; Original Paper ; Phospholipids ; Phosphorylcholine - analogs & derivatives ; Phosphorylcholine - pharmacology ; Physiological aspects ; Schistosoma ; Schistosoma mansoni ; Schistosoma mansoni - drug effects ; Schistosoma mansoni - physiology ; Schistosoma mansoni - ultrastructure ; Survival Analysis ; Time Factors ; Trypanosoma
Es parte de: Parasitology research (1987), 2012-06, Vol.110 (6), p.2465-2473
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descripción: Schistosomiasis is an infectious parasitic disease caused by helminths from the genus Schistosoma ; it affects over 200 million people globally and is endemic in 70 countries. In Brazil, 6 million individuals are infected with Schistosoma mansoni . Furthermore, as the prevalence of S. mansoni infections is increasing, approximately 26 million citizens in 19 Brazilian states are at risk for infection. Schistosomiasis disease control involves predominately the administration of a single drug, praziquantel. Although praziquantel exhibits chemotherapeutic efficacy and safety, its massive use in endemic zones, the possibility of the emergence of drug-resistant Schistosoma parasites, and the lack of another efficacious antischistosomal drug demand the discovery of new schistosomicidal compounds. First developed as anti-tumor drug, miltefosine is an alkylphospholipid derivative that exhibits bioactivity against Leishmania and Trypanosoma parasites, free-living protozoa, bacteria, and fungi. With its anti-parasite activity, miltefosine was the first orally administered drug against visceral and cutaneous leishmaniasis approved. Previously, by means of the MTT cytotoxic assay and a DNA fragmentation test, we verified that, at doses of 100 and 200 μM (40 and 80 μg/mL), miltefosine exhibited in vitro schistosomicidal activity against adult S. mansoni worms. Here, we present ultrastructural evidence of rapid, severe miltefosine-induced surface membrane damage in S. mansoni following drug treatment. The number of dead parasites was concentration- and time-dependent following miltefosine treatment. At a miltefosine concentration of 200 μM (∼80 μg/mL), in vitro parasite killing was initiated as early as 3 h post-incubation, and it was maximal after 24 h of treatment. The parasite death was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. According to our present results, miltefosine is very effective at inducing membrane destruction of S. mansoni with a short onset of pharmacological action.
Editor: Berlin/Heidelberg: Springer-Verlag
Idioma: Inglés

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Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms

Bertão, Humberto Gonçalves ; da Silva, Renata Alexandre Ramos ; Padilha, Rafael José R. ; de Azevedo Albuquerque, Mônica Camelo Pessôa ; Rádis-Baptista, Gandhi

Berlin/Heidelberg: Springer-Verlag

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