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Response to different benznidazole doses in animal models of chronic phase Chagas disease: a critical review.

Abstract Chagas disease is a protozoan infection that was identified over a century ago. No drugs are available to treat the indeterminate and determinate chronic phases of the disease. Success of a drug design is dependent on correct biological evaluation. Concerning new drug designs for Chagas disease, it is essential to first identify the most effective, existing, experimental chronic protocols that can be used for comparison purposes. Here, we present a literature review regarding experimental models with chronic Chagas disease to evaluate the efficacy of benznidazole (BZN). We searched literature published in PubMed and Web of Science databases, using these keywords: animal model, BZN, Chagas disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded articles involving acute phase animal models and/or those without BZN treatment. The selected studies were conducted using different BZN concentrations (10mg-100mg) involving several different periods (5-70 days). Concentrations and durations of use are directly related to side effects, but do not prevent chronic tissue lesions. BZN use during the late/chronic phases of Chagas disease is unable to eliminate amastigote forms present in infected tissues. This study suggests the administration of a lower BZN concentration (<100mg/kg/day) during the chronic phase of the animal model, as this had been reported to result in fewer side effects.
PMID
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Authors

Mayor MeshTerms

Dose-Response Relationship, Drug

Keywords
Journal Title revista da sociedade brasileira de medicina tropical
Publication Year Start




PMID- 29768544
OWN - NLM
STAT- MEDLINE
DCOM- 20180524
LR  - 20180524
IS  - 1678-9849 (Electronic)
IS  - 0037-8682 (Linking)
VI  - 51
IP  - 2
DP  - 2018 Mar-Apr
TI  - Response to different benznidazole doses in animal models of chronic phase Chagas
      disease: a critical review.
PG  - 133-140
LID - S0037-86822018000200133 [pii]
LID - 10.1590/0037-8682-0337-2017 [doi]
AB  - Chagas disease is a protozoan infection that was identified over a century ago.
      No drugs are available to treat the indeterminate and determinate chronic phases 
      of the disease. Success of a drug design is dependent on correct biological
      evaluation. Concerning new drug designs for Chagas disease, it is essential to
      first identify the most effective, existing, experimental chronic protocols that 
      can be used for comparison purposes. Here, we present a literature review
      regarding experimental models with chronic Chagas disease to evaluate the
      efficacy of benznidazole (BZN). We searched literature published in PubMed and
      Web of Science databases, using these keywords: animal model, BZN, Chagas
      disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded 
      articles involving acute phase animal models and/or those without BZN treatment. 
      The selected studies were conducted using different BZN concentrations
      (10mg-100mg) involving several different periods (5-70 days). Concentrations and 
      durations of use are directly related to side effects, but do not prevent chronic
      tissue lesions. BZN use during the late/chronic phases of Chagas disease is
      unable to eliminate amastigote forms present in infected tissues. This study
      suggests the administration of a lower BZN concentration (&lt;100mg/kg/day) during
      the chronic phase of the animal model, as this had been reported to result in
      fewer side effects.
FAU - Scarim, Caue Benito
AU  - Scarim CB
AD  - Departamento de Farmacos e Medicamentos, Faculdade de Ciencias Farmaceuticas,
      Universidade Estadual Paulista Julio de Mesquita Filho, Araraquara, SP, Brasil.
FAU - Ribeiro, Aline Rimoldi
AU  - Ribeiro AR
AD  - Departamento de Parasitologia, Instituto de Biologia, Universidade Estadual de
      Campinas, Campinas ,SP, Brasil.
FAU - Rosa, Joao Aristeu da
AU  - Rosa JAD
AD  - Departamento de Ciencias Biologicas, Faculdade de Ciencias Farmaceuticas,
      Universidade Estadual Paulista Julio de Mesquita Filho, Araraquara, SP, Brasil.
FAU - Chin, Chung Man
AU  - Chin CM
AD  - Departamento de Farmacos e Medicamentos, Faculdade de Ciencias Farmaceuticas,
      Universidade Estadual Paulista Julio de Mesquita Filho, Araraquara, SP, Brasil.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Brazil
TA  - Rev Soc Bras Med Trop
JT  - Revista da Sociedade Brasileira de Medicina Tropical
JID - 7507456
RN  - 0 (Nitroimidazoles)
RN  - 0 (Trypanocidal Agents)
RN  - YC42NRJ1ZD (benzonidazole)
SB  - IM
MH  - Animals
MH  - Chagas Disease/*drug therapy
MH  - Chronic Disease
MH  - Disease Models, Animal
MH  - *Dose-Response Relationship, Drug
MH  - Mice
MH  - Nitroimidazoles/*administration &amp; dosage
MH  - Trypanocidal Agents/*administration &amp; dosage
EDAT- 2018/05/17 06:00
MHDA- 2018/05/25 06:00
CRDT- 2018/05/17 06:00
PHST- 2017/09/28 00:00 [received]
PHST- 2018/04/18 00:00 [accepted]
PHST- 2018/05/17 06:00 [entrez]
PHST- 2018/05/17 06:00 [pubmed]
PHST- 2018/05/25 06:00 [medline]
AID - S0037-86822018000200133 [pii]
AID - 10.1590/0037-8682-0337-2017 [doi]
PST - ppublish
SO  - Rev Soc Bras Med Trop. 2018 Mar-Apr;51(2):133-140. doi:
      10.1590/0037-8682-0337-2017.