Benznidazole-induced ultrastructural and biochemical alterations in rat colon

Autores
Diaz, Edith Graciela; Rodriguez de Castro, Carmen; Montalto, Maria; Castro, Jose Alberto
Año de publicación
2000
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
AIM: To study the effects of benznidazole (Bz), a drug used in the chemotherapy of the acute and the intermediate phase of Chagas' disease, on the colon of rats. METHODS: Sprague Dawley male rats received Bz 100 mg/kg ig. After 24 h colons were examined by electron microscopy. Concentrations of Bz in colonic tissue were measured by HPLC. Bz nitroreduction was followed by the decrease in the drug concentration using spectrophotometry and HPLC or by covalent binding to proteins of reactive products formed under in vivo and in vitro conditions. RESULTS: Colon mucosa of Bz-treated rats showed intense ultrastructural alterations: abundant mucus secretion at the level of the Goblet cells and dilatation of the endoplasmic reticulum and the Golgi apparatus in epithelial cells. The concentration of Bz in tissue was (59 +/- 18) and (93 +/- 14) nmol/g (protein) 1 and 3 h after oral administration to rats, respectively. Colonic microsomes anaerobically activated Bz in the presence of NADPH. This activating nitroreductive pathway only involved a minor part of the total Bz and could not be detected spectrophotometrically or by HPLC analysis of the Bz consumed. Reactive metabolites that bound covalently to microsomal proteins were formed in this process. The covalent binding was also observed in vivo 1, 3, 6, and 24 h after administration of the labeled drug to rats. CONCLUSION: Reactive Bz metabolites produced during nitroreductive bioactivation of the drug in the colonic mucosa could interact with proteins and other cellular constituents to cause injury.
Fil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Rodriguez de Castro, Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Materia
Benznidazole
Benzene
Nitroreductases
Drug Therapy
Colonic Diseases
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:11336/71782
Acceder
id CONICETDig_76a663f34168bf4c90a2e7a18f43c524
oai_identifier_str oai:ri.conicet.gov.ar:11336/71782
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Benznidazole-induced ultrastructural and biochemical alterations in rat colonDiaz, Edith GracielaRodriguez de Castro, CarmenMontalto, MariaCastro, Jose AlbertoBenznidazoleBenzeneNitroreductasesDrug TherapyColonic Diseaseshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1AIM: To study the effects of benznidazole (Bz), a drug used in the chemotherapy of the acute and the intermediate phase of Chagas' disease, on the colon of rats. METHODS: Sprague Dawley male rats received Bz 100 mg/kg ig. After 24 h colons were examined by electron microscopy. Concentrations of Bz in colonic tissue were measured by HPLC. Bz nitroreduction was followed by the decrease in the drug concentration using spectrophotometry and HPLC or by covalent binding to proteins of reactive products formed under in vivo and in vitro conditions. RESULTS: Colon mucosa of Bz-treated rats showed intense ultrastructural alterations: abundant mucus secretion at the level of the Goblet cells and dilatation of the endoplasmic reticulum and the Golgi apparatus in epithelial cells. The concentration of Bz in tissue was (59 +/- 18) and (93 +/- 14) nmol/g (protein) 1 and 3 h after oral administration to rats, respectively. Colonic microsomes anaerobically activated Bz in the presence of NADPH. This activating nitroreductive pathway only involved a minor part of the total Bz and could not be detected spectrophotometrically or by HPLC analysis of the Bz consumed. Reactive metabolites that bound covalently to microsomal proteins were formed in this process. The covalent binding was also observed in vivo 1, 3, 6, and 24 h after administration of the labeled drug to rats. CONCLUSION: Reactive Bz metabolites produced during nitroreductive bioactivation of the drug in the colonic mucosa could interact with proteins and other cellular constituents to cause injury.Fil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Rodriguez de Castro, Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaWiley Blackwell Publishing, Inc2000-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71782Diaz, Edith Graciela; Rodriguez de Castro, Carmen; Montalto, Maria; Castro, Jose Alberto; Benznidazole-induced ultrastructural and biochemical alterations in rat colon; Wiley Blackwell Publishing, Inc; Acta Pharmacologica Sinica; 21; 11; 11-2000; 961-9660253-9756CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/aps/volumesinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:59:40Zoai:ri.conicet.gov.ar:11336/71782instacron: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:34982025-10-15 14:59:40.413CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Benznidazole-induced ultrastructural and biochemical alterations in rat colon
title Benznidazole-induced ultrastructural and biochemical alterations in rat colon
spellingShingle Benznidazole-induced ultrastructural and biochemical alterations in rat colon
Diaz, Edith Graciela
Benznidazole
Benzene
Nitroreductases
Drug Therapy
Colonic Diseases
title_short Benznidazole-induced ultrastructural and biochemical alterations in rat colon
title_full Benznidazole-induced ultrastructural and biochemical alterations in rat colon
title_fullStr Benznidazole-induced ultrastructural and biochemical alterations in rat colon
title_full_unstemmed Benznidazole-induced ultrastructural and biochemical alterations in rat colon
title_sort Benznidazole-induced ultrastructural and biochemical alterations in rat colon
dc.creator.none.fl_str_mv Diaz, Edith Graciela
Rodriguez de Castro, Carmen
Montalto, Maria
Castro, Jose Alberto
author Diaz, Edith Graciela
author_facet Diaz, Edith Graciela
Rodriguez de Castro, Carmen
Montalto, Maria
Castro, Jose Alberto
author_role author
author2 Rodriguez de Castro, Carmen
Montalto, Maria
Castro, Jose Alberto
author2_role author
author
author
dc.subject.none.fl_str_mv Benznidazole
Benzene
Nitroreductases
Drug Therapy
Colonic Diseases
topic Benznidazole
Benzene
Nitroreductases
Drug Therapy
Colonic Diseases
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv AIM: To study the effects of benznidazole (Bz), a drug used in the chemotherapy of the acute and the intermediate phase of Chagas' disease, on the colon of rats. METHODS: Sprague Dawley male rats received Bz 100 mg/kg ig. After 24 h colons were examined by electron microscopy. Concentrations of Bz in colonic tissue were measured by HPLC. Bz nitroreduction was followed by the decrease in the drug concentration using spectrophotometry and HPLC or by covalent binding to proteins of reactive products formed under in vivo and in vitro conditions. RESULTS: Colon mucosa of Bz-treated rats showed intense ultrastructural alterations: abundant mucus secretion at the level of the Goblet cells and dilatation of the endoplasmic reticulum and the Golgi apparatus in epithelial cells. The concentration of Bz in tissue was (59 +/- 18) and (93 +/- 14) nmol/g (protein) 1 and 3 h after oral administration to rats, respectively. Colonic microsomes anaerobically activated Bz in the presence of NADPH. This activating nitroreductive pathway only involved a minor part of the total Bz and could not be detected spectrophotometrically or by HPLC analysis of the Bz consumed. Reactive metabolites that bound covalently to microsomal proteins were formed in this process. The covalent binding was also observed in vivo 1, 3, 6, and 24 h after administration of the labeled drug to rats. CONCLUSION: Reactive Bz metabolites produced during nitroreductive bioactivation of the drug in the colonic mucosa could interact with proteins and other cellular constituents to cause injury.
Fil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Rodriguez de Castro, Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
description AIM: To study the effects of benznidazole (Bz), a drug used in the chemotherapy of the acute and the intermediate phase of Chagas' disease, on the colon of rats. METHODS: Sprague Dawley male rats received Bz 100 mg/kg ig. After 24 h colons were examined by electron microscopy. Concentrations of Bz in colonic tissue were measured by HPLC. Bz nitroreduction was followed by the decrease in the drug concentration using spectrophotometry and HPLC or by covalent binding to proteins of reactive products formed under in vivo and in vitro conditions. RESULTS: Colon mucosa of Bz-treated rats showed intense ultrastructural alterations: abundant mucus secretion at the level of the Goblet cells and dilatation of the endoplasmic reticulum and the Golgi apparatus in epithelial cells. The concentration of Bz in tissue was (59 +/- 18) and (93 +/- 14) nmol/g (protein) 1 and 3 h after oral administration to rats, respectively. Colonic microsomes anaerobically activated Bz in the presence of NADPH. This activating nitroreductive pathway only involved a minor part of the total Bz and could not be detected spectrophotometrically or by HPLC analysis of the Bz consumed. Reactive metabolites that bound covalently to microsomal proteins were formed in this process. The covalent binding was also observed in vivo 1, 3, 6, and 24 h after administration of the labeled drug to rats. CONCLUSION: Reactive Bz metabolites produced during nitroreductive bioactivation of the drug in the colonic mucosa could interact with proteins and other cellular constituents to cause injury.
publishDate 2000
dc.date.none.fl_str_mv 2000-11
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/11336/71782
Diaz, Edith Graciela; Rodriguez de Castro, Carmen; Montalto, Maria; Castro, Jose Alberto; Benznidazole-induced ultrastructural and biochemical alterations in rat colon; Wiley Blackwell Publishing, Inc; Acta Pharmacologica Sinica; 21; 11; 11-2000; 961-966
0253-9756
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71782
identifier_str_mv Diaz, Edith Graciela; Rodriguez de Castro, Carmen; Montalto, Maria; Castro, Jose Alberto; Benznidazole-induced ultrastructural and biochemical alterations in rat colon; Wiley Blackwell Publishing, Inc; Acta Pharmacologica Sinica; 21; 11; 11-2000; 961-966
0253-9756
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/aps/volumes
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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 13.22299

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