Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease

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dc.citation.titlePLOS Neglected Tropical Diseaseses
dc.citation.volume11(12)es
dc.creatorRial, Marcela S.
dc.creatorScalise, María L.
dc.creatorArrúa, Eva Carolina
dc.creatorEsteva, Mónica I.
dc.creatorSalomon, Claudio
dc.creatorFichera, Laura E.
dc.date.accessioned2021-02-25T15:12:49Z
dc.date.available2021-02-25T15:12:49Z
dc.date.issued2017-12-21
dc.descriptionBackground Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required. Methodology In this study, the efficacy of orally administered low doses of benznidazole (BNZ) nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN) that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps) and raw BNZ (R-BNZ) were also evaluated. Principal findings T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi)), while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day) and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50–100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production. Conclusions Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further evidence for the optimization of dosage regimens to treat Chagas disease.es
dc.descriptionPara citar este articulo: Rial MS, Scalise ML, Arrúa EC, Esteva MI, Salomon CJ, Fichera LE (2017) Elucidating the impact of low doses of nano-formulated benznidazole in acute experimental Chagas disease. PLoS Negl Trop Dis 11(12): e0006119. https://doi.org/10.1371/journal.pntd.0006119
dc.description.filFil: Rial, Marcela S. Ministerio de Salud. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G. Malbrán”. Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben”; Argentina.es
dc.description.filFil: Scalise, María L. Ministerio de Salud. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G. Malbrán”. Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben”; Argentina.es
dc.description.filFil: Arrúa, Eva Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Farmacia. Área Técnica Farmacéutica; Argentina.es
dc.description.filFil: Esteva, Mónica I. Ministerio de Salud. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G. Malbrán”. Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben”; Argentina.es
dc.description.filFil: Salomon, Claudio. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Farmacia. Área Técnica Farmacéutica; Argentina.es
dc.description.filFil: Salomon, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina.es
dc.description.filFil: Fichera, Laura E. Ministerio de Salud. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G. Malbrán”. Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben”; Argentinaes
dc.description.filFil: Fichera, Laura E. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina.es
dc.description.sponsorshipMinisterio de Salud. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G. Malbrán”- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP 483, PIP 194 y FOCANLIS 2011es
dc.description.sponsorshipUniversidad Nacional de Rosario (UNR)- Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 1078es
dc.formatapplication/pdf
dc.format.extent1-16es
dc.identifier.issn1935-2735es
dc.identifier.urihttp://hdl.handle.net/2133/19919
dc.language.isoenges
dc.publisherPublic Library of Science (PLOS)es
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pntd.0006119es
dc.relation.publisherversionhttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006119es
dc.rightsopenAccesses
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.holderRial, Marcela S.es
dc.rights.holderScalise, María L.es
dc.rights.holderArrúa, Eva Carolinaes
dc.rights.holderEsteva, Mónica I.es
dc.rights.holderSalomon, Claudioes
dc.rights.holderFichera, Laura E.es
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectChagas Diseasees
dc.subjectBenznidazolees
dc.subjectNanoparticleses
dc.subjectNeglected Diseaseses
dc.subjectTrypanosoma cruzies
dc.titleElucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas diseasees
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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