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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/71782
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:03:15Zoai: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:34982025-09-29 10:03:15.675CONICET 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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1844613846136782848 |
score |
13.070432 |