Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole

Autores
Montalto, Maria; Bartel, L. C.; Castro, Jose Alberto
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5–6 weeks old (125–150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.
Fil: Montalto, Maria. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bartel, L. C.. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Jose Alberto. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; Argentina
Materia
Alcohol Drinking
Nifurtimox
Benznidazole
Liver Microsomes
Nitroreduction
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:11336/7506
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7506
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and BenznidazoleMontalto, MariaBartel, L. C.Castro, Jose AlbertoAlcohol DrinkingNifurtimoxBenznidazoleLiver MicrosomesNitroreductionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5–6 weeks old (125–150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.Fil: Montalto, Maria. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bartel, L. C.. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, Jose Alberto. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; ArgentinaSage Publications Ltd2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7506Montalto, Maria; Bartel, L. C.; Castro, Jose Alberto; Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole; Sage Publications Ltd; Human and Experimental Toxicoloxy; 32; 12; 12-2013; 1305-13100960-3271enginfo:eu-repo/semantics/altIdentifier/url/http://het.sagepub.com/content/32/12/1305.longinfo:eu-repo/semantics/altIdentifier/doi/10.1177/0960327113485254info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:58Zoai:ri.conicet.gov.ar:11336/7506instacron: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:34982025-09-03 10:07:59.03CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
title Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
spellingShingle Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
Montalto, Maria
Alcohol Drinking
Nifurtimox
Benznidazole
Liver Microsomes
Nitroreduction
title_short Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
title_full Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
title_fullStr Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
title_full_unstemmed Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
title_sort Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole
dc.creator.none.fl_str_mv Montalto, Maria
Bartel, L. C.
Castro, Jose Alberto
author Montalto, Maria
author_facet Montalto, Maria
Bartel, L. C.
Castro, Jose Alberto
author_role author
author2 Bartel, L. C.
Castro, Jose Alberto
author2_role author
author
dc.subject.none.fl_str_mv Alcohol Drinking
Nifurtimox
Benznidazole
Liver Microsomes
Nitroreduction
topic Alcohol Drinking
Nifurtimox
Benznidazole
Liver Microsomes
Nitroreduction
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5–6 weeks old (125–150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.
Fil: Montalto, Maria. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bartel, L. C.. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Jose Alberto. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; Argentina
description Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5–6 weeks old (125–150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
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/11336/7506
Montalto, Maria; Bartel, L. C.; Castro, Jose Alberto; Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole; Sage Publications Ltd; Human and Experimental Toxicoloxy; 32; 12; 12-2013; 1305-1310
0960-3271
url http://hdl.handle.net/11336/7506
identifier_str_mv Montalto, Maria; Bartel, L. C.; Castro, Jose Alberto; Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of Nifurtimox and Benznidazole; Sage Publications Ltd; Human and Experimental Toxicoloxy; 32; 12; 12-2013; 1305-1310
0960-3271
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://het.sagepub.com/content/32/12/1305.long
info:eu-repo/semantics/altIdentifier/doi/10.1177/0960327113485254
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
dc.publisher.none.fl_str_mv Sage Publications Ltd
publisher.none.fl_str_mv Sage Publications Ltd
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
_version_ 1842270026130784256
score 13.13397

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