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Impact of levamisole in co-administration with benznidazole on experimental Chagas disease

  • Marianne Rocha Simões-Silva (a1), Raiza Brandão Peres (a1), Constança Britto (a2), Cynthia Machado Cascabulho (a3), Gabriel de Melo Oliveira (a1), Aline Nefertiti da Gama (a1), Cristiane França da Silva (a1), Karine Lima da Costa (a1), Paula Finamore Araújo (a2), Jerônimo Diego de Souza Campos (a1), Marcos Meuser Batista (a1), Kelly Cristina Demarque (a1), Otacílio da Cruz Moreira (a2) and Maria de Nazaré Correia Soeiro (a1)...

Abstract

Levamisole (Lms) is an anthelminthic drug with immunomodulatory activity. Chagas disease (CD) is caused by Trypanosoma cruzi and there is very low access to the drugs available, benznidazole (Bz) and nifurtimox, both far from ideal. In a drug-repurposing strategy to test potential activity as antiparasitic and immunomodulatory agent for CD, Lms was assayed on acute T. cruzi murine infection, alone and in co-administration with Bz. During protocol standardization, 100 and 10 mpk of Bz given for five consecutive days resulted in parasitaemia suppression and 100% animal survival only with the highest dose. Flow cytometry showed that both optimal (100 mpk) and suboptimal (10 mpk) doses of Bz equally decreased the plasma levels of cytokines commonly elevated in this acute infection model. Lms alone (10–0.5 mpk) did not decrease parasitaemia nor mortality rates. Co-administration was investigated using the suboptimal dose of Bz and different doses of Lms. While Bz 10 mpk did not alter parasitaemia, the combo partially reduced it but only slightly promoted animal survival. This effect could be related to Th1-response modulation since interleukin-6 and interferon-γ were higher after treatment with the combo.

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Corresponding author

Author for correspondence: Maria de Nazaré Correia Soeiro, E-mail: soeiro@ioc.fioruz.br

References

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Impact of levamisole in co-administration with benznidazole on experimental Chagas disease

  • Marianne Rocha Simões-Silva (a1), Raiza Brandão Peres (a1), Constança Britto (a2), Cynthia Machado Cascabulho (a3), Gabriel de Melo Oliveira (a1), Aline Nefertiti da Gama (a1), Cristiane França da Silva (a1), Karine Lima da Costa (a1), Paula Finamore Araújo (a2), Jerônimo Diego de Souza Campos (a1), Marcos Meuser Batista (a1), Kelly Cristina Demarque (a1), Otacílio da Cruz Moreira (a2) and Maria de Nazaré Correia Soeiro (a1)...

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