Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease

Autores
Davies, Carolina; Cardozo, Rubén Marino; Sánchez Negrette, Olga; Mora, Maria Celia; Chung, Man Chin; Basombrio, Miguel Angel Manuel
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.
Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
Fil: Cardozo, Rubén Marino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Sánchez Negrette, Olga. Ministerio de Salud Pública de Salta. Centro de Salud Nº15; Argentina
Fil: Mora, Maria Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
Fil: Chung, Man Chin. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil
Fil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
Materia
Hidroximetilnitrofurazona
Murine Model
Chagas Disease
Anti-T. Cruzi Agent
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/16249
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/16249
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ DiseaseDavies, CarolinaCardozo, Rubén MarinoSánchez Negrette, OlgaMora, Maria CeliaChung, Man ChinBasombrio, Miguel Angel ManuelHidroximetilnitrofurazonaMurine ModelChagas DiseaseAnti-T. Cruzi Agenthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; ArgentinaFil: Cardozo, Rubén Marino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Sánchez Negrette, Olga. Ministerio de Salud Pública de Salta. Centro de Salud Nº15; ArgentinaFil: Mora, Maria Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; ArgentinaFil: Chung, Man Chin. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; ArgentinaAmerican Society For Microbiology2010-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16249Davies, Carolina; Cardozo, Rubén Marino; Sánchez Negrette, Olga; Mora, Maria Celia; Chung, Man Chin; et al.; Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease; American Society For Microbiology; Antimicrobial Agents And Chemotherapy; 54; 9; 9-2010; 3584-35890066-4804enginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01451-09info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/54/9/3584info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:50:14Zoai:ri.conicet.gov.ar:11336/16249instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-05 09:50:14.709CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
title Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
spellingShingle Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
Davies, Carolina
Hidroximetilnitrofurazona
Murine Model
Chagas Disease
Anti-T. Cruzi Agent
title_short Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
title_full Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
title_fullStr Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
title_full_unstemmed Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
title_sort Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease
dc.creator.none.fl_str_mv Davies, Carolina
Cardozo, Rubén Marino
Sánchez Negrette, Olga
Mora, Maria Celia
Chung, Man Chin
Basombrio, Miguel Angel Manuel
author Davies, Carolina
author_facet Davies, Carolina
Cardozo, Rubén Marino
Sánchez Negrette, Olga
Mora, Maria Celia
Chung, Man Chin
Basombrio, Miguel Angel Manuel
author_role author
author2 Cardozo, Rubén Marino
Sánchez Negrette, Olga
Mora, Maria Celia
Chung, Man Chin
Basombrio, Miguel Angel Manuel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Hidroximetilnitrofurazona
Murine Model
Chagas Disease
Anti-T. Cruzi Agent
topic Hidroximetilnitrofurazona
Murine Model
Chagas Disease
Anti-T. Cruzi Agent
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.
Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
Fil: Cardozo, Rubén Marino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Sánchez Negrette, Olga. Ministerio de Salud Pública de Salta. Centro de Salud Nº15; Argentina
Fil: Mora, Maria Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
Fil: Chung, Man Chin. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil
Fil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
description The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.
publishDate 2010
dc.date.none.fl_str_mv 2010-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/16249
Davies, Carolina; Cardozo, Rubén Marino; Sánchez Negrette, Olga; Mora, Maria Celia; Chung, Man Chin; et al.; Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease; American Society For Microbiology; Antimicrobial Agents And Chemotherapy; 54; 9; 9-2010; 3584-3589
0066-4804
url http://hdl.handle.net/11336/16249
identifier_str_mv Davies, Carolina; Cardozo, Rubén Marino; Sánchez Negrette, Olga; Mora, Maria Celia; Chung, Man Chin; et al.; Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas’ Disease; American Society For Microbiology; Antimicrobial Agents And Chemotherapy; 54; 9; 9-2010; 3584-3589
0066-4804
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01451-09
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/54/9/3584
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society For Microbiology
publisher.none.fl_str_mv American Society For Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.087074

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