Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet

Autores
Diaz Gomez, Maria Isabel; Fanelli, Silvia Laura; Delgado, Aurora Maria; Castro, Jose Alberto; Castro, Gerardo Daniel
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH); N-nitrosodimethylamine (NDMA); carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via CYP2E1-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol containing liquid diet, exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The NADPH-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response of them to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited p-nitrophenol hydroxylase activity smaller than the one present in microsomes but inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4 that was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.
Fil: Diaz Gomez, Maria Isabel. 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. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Delgado, Aurora Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Materia
Ethanol
Nuclei
Nems
Cyp2e1
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:11336/28442
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/28442
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid dietDiaz Gomez, Maria IsabelFanelli, Silvia LauraDelgado, Aurora MariaCastro, Jose AlbertoCastro, Gerardo DanielEthanolNucleiNemsCyp2e1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH); N-nitrosodimethylamine (NDMA); carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via CYP2E1-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol containing liquid diet, exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The NADPH-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response of them to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited p-nitrophenol hydroxylase activity smaller than the one present in microsomes but inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4 that was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.Fil: Diaz Gomez, Maria Isabel. 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. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Delgado, Aurora Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaSage Publications2006-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/28442Diaz Gomez, Maria Isabel; Fanelli, Silvia Laura; Delgado, Aurora Maria; Castro, Jose Alberto; Castro, Gerardo Daniel; Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet; Sage Publications; Toxicology And Industrial Health; 22; 9; 1-10-2006; 367-3740748-2337CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/abs/10.1177/0748233706070982info:eu-repo/semantics/altIdentifier/doi/10.1177/0748233706070982info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:03:12Zoai:ri.conicet.gov.ar:11336/28442instacron: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:34982025-09-10 13:03:13.189CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
title Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
spellingShingle Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
Diaz Gomez, Maria Isabel
Ethanol
Nuclei
Nems
Cyp2e1
title_short Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
title_full Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
title_fullStr Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
title_full_unstemmed Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
title_sort Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
dc.creator.none.fl_str_mv Diaz Gomez, Maria Isabel
Fanelli, Silvia Laura
Delgado, Aurora Maria
Castro, Jose Alberto
Castro, Gerardo Daniel
author Diaz Gomez, Maria Isabel
author_facet Diaz Gomez, Maria Isabel
Fanelli, Silvia Laura
Delgado, Aurora Maria
Castro, Jose Alberto
Castro, Gerardo Daniel
author_role author
author2 Fanelli, Silvia Laura
Delgado, Aurora Maria
Castro, Jose Alberto
Castro, Gerardo Daniel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ethanol
Nuclei
Nems
Cyp2e1
topic Ethanol
Nuclei
Nems
Cyp2e1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH); N-nitrosodimethylamine (NDMA); carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via CYP2E1-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol containing liquid diet, exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The NADPH-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response of them to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited p-nitrophenol hydroxylase activity smaller than the one present in microsomes but inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4 that was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.
Fil: Diaz Gomez, Maria Isabel. 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. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Delgado, Aurora Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina
description In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH); N-nitrosodimethylamine (NDMA); carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via CYP2E1-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol containing liquid diet, exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The NADPH-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response of them to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited p-nitrophenol hydroxylase activity smaller than the one present in microsomes but inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4 that was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.
publishDate 2006
dc.date.none.fl_str_mv 2006-10-01
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/11336/28442
Diaz Gomez, Maria Isabel; Fanelli, Silvia Laura; Delgado, Aurora Maria; Castro, Jose Alberto; Castro, Gerardo Daniel; Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet; Sage Publications; Toxicology And Industrial Health; 22; 9; 1-10-2006; 367-374
0748-2337
CONICET Digital
CONICET
url http://hdl.handle.net/11336/28442
identifier_str_mv Diaz Gomez, Maria Isabel; Fanelli, Silvia Laura; Delgado, Aurora Maria; Castro, Jose Alberto; Castro, Gerardo Daniel; Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet; Sage Publications; Toxicology And Industrial Health; 22; 9; 1-10-2006; 367-374
0748-2337
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://journals.sagepub.com/doi/abs/10.1177/0748233706070982
info:eu-repo/semantics/altIdentifier/doi/10.1177/0748233706070982
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
application/pdf
dc.publisher.none.fl_str_mv Sage Publications
publisher.none.fl_str_mv Sage Publications
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 12.993085

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