Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease
Background 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 sid...
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| Autores principales: | , , , , , |
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| Formato: | article artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
Public Library of Science (PLOS)
2021
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/2133/19919 http://hdl.handle.net/2133/19919 |
| Aporte de: |
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I15-R121-2133-19919 |
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| record_format |
dspace |
| institution |
Universidad Nacional de Rosario |
| institution_str |
I-15 |
| repository_str |
R-121 |
| collection |
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
Chagas Disease Benznidazole Nanoparticles Neglected Diseases Trypanosoma cruzi |
| spellingShingle |
Chagas Disease Benznidazole Nanoparticles Neglected Diseases Trypanosoma cruzi Rial, Marcela S. Scalise, María L. Arrúa, Eva Carolina Esteva, Mónica I. Salomon, Claudio Fichera, Laura E. Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| topic_facet |
Chagas Disease Benznidazole Nanoparticles Neglected Diseases Trypanosoma cruzi |
| description |
Background
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. |
| format |
article artículo publishedVersion |
| author |
Rial, Marcela S. Scalise, María L. Arrúa, Eva Carolina Esteva, Mónica I. Salomon, Claudio Fichera, Laura E. |
| author_facet |
Rial, Marcela S. Scalise, María L. Arrúa, Eva Carolina Esteva, Mónica I. Salomon, Claudio Fichera, Laura E. |
| author_sort |
Rial, Marcela S. |
| title |
Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| title_short |
Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| title_full |
Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| title_fullStr |
Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| title_full_unstemmed |
Elucidating the impact of low doses of nanoformulated benznidazole in acute experimental Chagas disease |
| title_sort |
elucidating the impact of low doses of nanoformulated benznidazole in acute experimental chagas disease |
| publisher |
Public Library of Science (PLOS) |
| publishDate |
2021 |
| url |
http://hdl.handle.net/2133/19919 http://hdl.handle.net/2133/19919 |
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