Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi.
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/12050 https://doi.org/10.1128/AAC.02264-18 |
Resumo: | Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi. The in vitro effect of allopurinol plus benznidazole or nifurtimox on intracellular amastigotes in infected H9c2 cells was assessed in a 72-h assay. The interactions were classified as synergic for both allopurinol-nifurtimox (sums of fractional inhibitory concentrations [FICs] 0.49 0.08) and allopurinol-benznidazole (FICs 0.48 0.09). In the next step, infected Swiss mice were treated with allopurinol at 30, 60, and 90 mg/kg of body weight and with benznidazole at 25, 50, and 75 mg/kg in monotherapy and in combination at the same doses; as a reference treatment, another group of animals received benznidazole at 100 mg/kg. Allopurinol in monotherapy led to a smaller or nil effect in the reduction of parasite load and mortality rate. Treatment with benznidazole at suboptimal doses induced a transient suppression of parasitaemia with subsequent relapse in all animals treated with 25 and 50 mg/kg and in 80% of those that received 75 mg/kg. Administration of the drugs in combination significantly increased the cure rate to 60 to 100% among mice treated with benznidazole at 75 mg/kg plus 30, 60, or 90 mg/kg of allopurinol. These results show a positive interaction between allopurinol and benznidazole, and since both drugs are commercially available, their use in combination may be considered for the assessment in the treatment of Chagas disease patients. |
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Mazzeti, Ana LiaDiniz, Lívia de FigueiredoGonçalves, Karolina RibeiroWonDollinger, Ruan SchottMartins, Tassiane Assíria FontesRibeiro, IsabelaBahia, Maria Terezinha2020-04-09T21:19:45Z2020-04-09T21:19:45Z2019MAZZETI, A. L. Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. Antimicrobial agents and Chemotherapy, v. 63, p. e02264-18, jun. 2019. Disponível em: <https://aac.asm.org/content/63/6/e02264-18.long>. Acesso em: 10 fev. 2020.1098-6596http://www.repositorio.ufop.br/handle/123456789/12050https://doi.org/10.1128/AAC.02264-18Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi. The in vitro effect of allopurinol plus benznidazole or nifurtimox on intracellular amastigotes in infected H9c2 cells was assessed in a 72-h assay. The interactions were classified as synergic for both allopurinol-nifurtimox (sums of fractional inhibitory concentrations [FICs] 0.49 0.08) and allopurinol-benznidazole (FICs 0.48 0.09). In the next step, infected Swiss mice were treated with allopurinol at 30, 60, and 90 mg/kg of body weight and with benznidazole at 25, 50, and 75 mg/kg in monotherapy and in combination at the same doses; as a reference treatment, another group of animals received benznidazole at 100 mg/kg. Allopurinol in monotherapy led to a smaller or nil effect in the reduction of parasite load and mortality rate. Treatment with benznidazole at suboptimal doses induced a transient suppression of parasitaemia with subsequent relapse in all animals treated with 25 and 50 mg/kg and in 80% of those that received 75 mg/kg. Administration of the drugs in combination significantly increased the cure rate to 60 to 100% among mice treated with benznidazole at 75 mg/kg plus 30, 60, or 90 mg/kg of allopurinol. These results show a positive interaction between allopurinol and benznidazole, and since both drugs are commercially available, their use in combination may be considered for the assessment in the treatment of Chagas disease patients.This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Fonte: o próprio artigo.info:eu-repo/semantics/openAccessChagas diseaseBenznidazoleChemotherapyCombination therapySynergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-8924http://www.repositorio.ufop.br/bitstream/123456789/12050/2/license.txt62604f8d955274beb56c80ce1ee5dcaeMD52ORIGINALARTIGO_SinergicEffectAllopurinol.pdfARTIGO_SinergicEffectAllopurinol.pdfapplication/pdf1411293http://www.repositorio.ufop.br/bitstream/123456789/12050/1/ARTIGO_SinergicEffectAllopurinol.pdf06a8ad7243e2f32e2b49b284c5462dfbMD51123456789/120502020-04-09 17:19:45.635oai:localhost: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ório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332020-04-09T21:19:45Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
title |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
spellingShingle |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. Mazzeti, Ana Lia Chagas disease Benznidazole Chemotherapy Combination therapy |
title_short |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
title_full |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
title_fullStr |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
title_full_unstemmed |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
title_sort |
Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. |
author |
Mazzeti, Ana Lia |
author_facet |
Mazzeti, Ana Lia Diniz, Lívia de Figueiredo Gonçalves, Karolina Ribeiro WonDollinger, Ruan Schott Martins, Tassiane Assíria Fontes Ribeiro, Isabela Bahia, Maria Terezinha |
author_role |
author |
author2 |
Diniz, Lívia de Figueiredo Gonçalves, Karolina Ribeiro WonDollinger, Ruan Schott Martins, Tassiane Assíria Fontes Ribeiro, Isabela Bahia, Maria Terezinha |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Mazzeti, Ana Lia Diniz, Lívia de Figueiredo Gonçalves, Karolina Ribeiro WonDollinger, Ruan Schott Martins, Tassiane Assíria Fontes Ribeiro, Isabela Bahia, Maria Terezinha |
dc.subject.por.fl_str_mv |
Chagas disease Benznidazole Chemotherapy Combination therapy |
topic |
Chagas disease Benznidazole Chemotherapy Combination therapy |
description |
Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi. The in vitro effect of allopurinol plus benznidazole or nifurtimox on intracellular amastigotes in infected H9c2 cells was assessed in a 72-h assay. The interactions were classified as synergic for both allopurinol-nifurtimox (sums of fractional inhibitory concentrations [FICs] 0.49 0.08) and allopurinol-benznidazole (FICs 0.48 0.09). In the next step, infected Swiss mice were treated with allopurinol at 30, 60, and 90 mg/kg of body weight and with benznidazole at 25, 50, and 75 mg/kg in monotherapy and in combination at the same doses; as a reference treatment, another group of animals received benznidazole at 100 mg/kg. Allopurinol in monotherapy led to a smaller or nil effect in the reduction of parasite load and mortality rate. Treatment with benznidazole at suboptimal doses induced a transient suppression of parasitaemia with subsequent relapse in all animals treated with 25 and 50 mg/kg and in 80% of those that received 75 mg/kg. Administration of the drugs in combination significantly increased the cure rate to 60 to 100% among mice treated with benznidazole at 75 mg/kg plus 30, 60, or 90 mg/kg of allopurinol. These results show a positive interaction between allopurinol and benznidazole, and since both drugs are commercially available, their use in combination may be considered for the assessment in the treatment of Chagas disease patients. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-04-09T21:19:45Z |
dc.date.available.fl_str_mv |
2020-04-09T21:19:45Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MAZZETI, A. L. Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. Antimicrobial agents and Chemotherapy, v. 63, p. e02264-18, jun. 2019. Disponível em: <https://aac.asm.org/content/63/6/e02264-18.long>. Acesso em: 10 fev. 2020. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/12050 |
dc.identifier.issn.none.fl_str_mv |
1098-6596 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1128/AAC.02264-18 |
identifier_str_mv |
MAZZETI, A. L. Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against Trypanosoma cruzi. Antimicrobial agents and Chemotherapy, v. 63, p. e02264-18, jun. 2019. Disponível em: <https://aac.asm.org/content/63/6/e02264-18.long>. Acesso em: 10 fev. 2020. 1098-6596 |
url |
http://www.repositorio.ufop.br/handle/123456789/12050 https://doi.org/10.1128/AAC.02264-18 |
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eng |
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