Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus

Autores
Castro, Jose Alberto; Montalto, Maria; Fanelli, Silvia Laura; Cignoli de Ferreyra, Elida; Diaz, Edith Graciela; Castro, Jose Alberto
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas’ disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague–Dawley male rats (240–260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4±4.0 and 149.2±14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.
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; Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Fanelli, Silvia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Cignoli de Ferreyra, Elida. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Materia
Benznidazole
Chagas Disease
Toxic Side Effects
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:11336/32597
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/32597
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Benznidazole-induced ultrastructural and biochemical alterations in rat esophagusCastro, Jose AlbertoMontalto, MariaFanelli, Silvia LauraCignoli de Ferreyra, ElidaDiaz, Edith GracielaCastro, Jose AlbertoBenznidazoleChagas DiseaseToxic Side Effectshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas’ disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague–Dawley male rats (240–260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4±4.0 and 149.2±14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.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; ArgentinaFil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Fanelli, Silvia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Cignoli de Ferreyra, Elida. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaElsevier Ireland2003-09info: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/11336/32597Castro, Jose Alberto; Montalto, Maria; Fanelli, Silvia Laura; Cignoli de Ferreyra, Elida; Diaz, Edith Graciela; et al.; Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus; Elsevier Ireland; Toxicology; 191; 2-3; 9-2003; 189-1980300-483XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0300483X03002622info:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(03)00262-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:27Zoai:ri.conicet.gov.ar:11336/32597instacron: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 09:58:27.895CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
title Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
spellingShingle Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
Castro, Jose Alberto
Benznidazole
Chagas Disease
Toxic Side Effects
title_short Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
title_full Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
title_fullStr Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
title_full_unstemmed Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
title_sort Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus
dc.creator.none.fl_str_mv Castro, Jose Alberto
Montalto, Maria
Fanelli, Silvia Laura
Cignoli de Ferreyra, Elida
Diaz, Edith Graciela
Castro, Jose Alberto
author Castro, Jose Alberto
author_facet Castro, Jose Alberto
Montalto, Maria
Fanelli, Silvia Laura
Cignoli de Ferreyra, Elida
Diaz, Edith Graciela
author_role author
author2 Montalto, Maria
Fanelli, Silvia Laura
Cignoli de Ferreyra, Elida
Diaz, Edith Graciela
author2_role author
author
author
author
dc.subject.none.fl_str_mv Benznidazole
Chagas Disease
Toxic Side Effects
topic Benznidazole
Chagas Disease
Toxic Side Effects
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas’ disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague–Dawley male rats (240–260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4±4.0 and 149.2±14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.
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; Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Fanelli, Silvia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Cignoli de Ferreyra, Elida. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
description Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas’ disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague–Dawley male rats (240–260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4±4.0 and 149.2±14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.
publishDate 2003
dc.date.none.fl_str_mv 2003-09
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/11336/32597
Castro, Jose Alberto; Montalto, Maria; Fanelli, Silvia Laura; Cignoli de Ferreyra, Elida; Diaz, Edith Graciela; et al.; Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus; Elsevier Ireland; Toxicology; 191; 2-3; 9-2003; 189-198
0300-483X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32597
identifier_str_mv Castro, Jose Alberto; Montalto, Maria; Fanelli, Silvia Laura; Cignoli de Ferreyra, Elida; Diaz, Edith Graciela; et al.; Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus; Elsevier Ireland; Toxicology; 191; 2-3; 9-2003; 189-198
0300-483X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0300483X03002622
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(03)00262-2
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 Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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 13.069144

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