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Elucidating the impact of low doses of nano-formulated benznidazole in acute experimental Chagas disease.

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos neglected tropical diseases
Publication Year Start




PMID- 29267280
OWN - NLM
STAT- In-Data-Review
LR  - 20180105
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 12
DP  - 2017 Dec
TI  - Elucidating the impact of low doses of nano-formulated benznidazole in acute
      experimental Chagas disease.
PG  - e0006119
LID - 10.1371/journal.pntd.0006119 [doi]
AB  - 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.
FAU - Rial, Marcela S
AU  - Rial MS
AD  - Instituto Nacional de Parasitologia "Dr. Mario Fatala Chaben", ANLIS "Dr. Carlos 
      G. Malbran", Ministerio de Salud, Buenos Aires, Argentina.
FAU - Scalise, Maria L
AU  - Scalise ML
AD  - Instituto Nacional de Parasitologia "Dr. Mario Fatala Chaben", ANLIS "Dr. Carlos 
      G. Malbran", Ministerio de Salud, Buenos Aires, Argentina.
FAU - Arrua, Eva C
AU  - Arrua EC
AD  - Area Tecnica Farmaceutica, Departamento de Farmacia, Facultad de Ciencias
      Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Rosario, Argentina.
FAU - Esteva, Monica I
AU  - Esteva MI
AD  - Instituto Nacional de Parasitologia "Dr. Mario Fatala Chaben", ANLIS "Dr. Carlos 
      G. Malbran", Ministerio de Salud, Buenos Aires, Argentina.
FAU - Salomon, Claudio J
AU  - Salomon CJ
AUID- ORCID: http://orcid.org/0000-0003-1599-790X
AD  - Area Tecnica Farmaceutica, Departamento de Farmacia, Facultad de Ciencias
      Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Rosario, Argentina.
AD  - Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos
      Aires, Argentina.
FAU - Fichera, Laura E
AU  - Fichera LE
AD  - Instituto Nacional de Parasitologia "Dr. Mario Fatala Chaben", ANLIS "Dr. Carlos 
      G. Malbran", Ministerio de Salud, Buenos Aires, Argentina.
AD  - Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos
      Aires, Argentina.
LA  - eng
PT  - Journal Article
DEP - 20171221
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:00
CRDT- 2017/12/22 06:00
PHST- 2017/06/30 00:00 [received]
PHST- 2017/11/17 00:00 [accepted]
PHST- 2018/01/05 00:00 [revised]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:00 [medline]
PHST- 2017/12/22 06:00 [entrez]
AID - 10.1371/journal.pntd.0006119 [doi]
AID - PNTD-D-17-01063 [pii]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Dec 21;11(12):e0006119. doi:
      10.1371/journal.pntd.0006119. eCollection 2017 Dec.