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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols
PLoS Neglected Tropical Diseases, Volume 3, No. 7, Article e477, Year 2009
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Description
Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings:Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11th to 17th day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions:The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis. © 2009 Corrêa Soares et al.
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Authors & Co-Authors
Corrêa Soares, Juliana B.R.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Menezes, Diego Silva
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Vannier-Santos, Marcos André
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Ferreira-Pereira, A.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Almeida, Giulliana Tessarin
Brazil, Sao Paulo
Universidade de São Paulo
Venancio, Thiago M.
Brazil, Sao Paulo
Universidade de São Paulo
United States, Bethesda
National Library of Medicine Nlm
Verjovski-Almeida, Sergio
Brazil, Sao Paulo
Universidade de São Paulo
Zishiri, Vincent K.
South Africa, Cape Town
University of Cape Town
Kuter, David
South Africa, Cape Town
University of Cape Town
Hunter, Roger
South Africa, Cape Town
University of Cape Town
Egan, Timothy John
South Africa, Cape Town
University of Cape Town
Oliveira, Marcus F.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Statistics
Citations: 76
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pntd.0000477
Research Areas
Genetics And Genomics
Infectious Diseases
Participants Gender
Male
Female