Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations

Autores
Fernandez Villamil, Silvia Hebe; Stoppani, Andrés O. M.; Dubin, Marta
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The lipophilic o-naphthoquinones beta-lapachone and structural analogous quinones (CG quinones) are proposed as cytostatic, trypanocidal and antiviral agents. With rat liver microsomal NAD(P)H cytochrome P450 reductase or cytosol flavoenzyme DTD, these quinones constitute redox systems that in the presence of oxygen generate ROS. o-Naphthoquinones redox cycling, catalyzed by the NADPH cytochrome P450 reductase, generate in microsomal liver preparations: (a) semiquinone free radicals, (b) ROS and (c) inhibition of cytochrome P450-dependent reactions, exerting cytotoxic effects. Hydroquinones, are the immediate products of quinones reduction by the DTD-dependent systems. Three types of hydroquinones formed by that reaction have been proposed by Cadenas: (a) redox stable hydroquinones; (b) redox labile hydroquinones that subsequently reoxidize, with formation of semiquinone and ROS and (c) redox-labile semiquinones that immediately rearrange to potent electrophils undergoing biological alkylating reactions. Our observations with beta-lapachone and related o-naphthoquinones indicate that the corresponding hydroquinones must be included in the second group in agreement with (a) the semiquinone spectrum, demonstrated by ESR spectroscopy; (b) semiquinone (or quinone) production demonstrated by optical spectroscopy and; (c) the effect of dicoumarol on the quinone redox-cycling and oxygen consumption by the NADPH/o-naphthoquinone/DTD system. These reactions associated to DTD activity seem to rule out the contention proposing DTD as an antioxidant enzyme protecting against quinone toxicity.
Fil: Fernandez Villamil, Silvia Hebe. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Stoppani, Andrés O. M.. Universidad de Buenos Aires; Argentina
Fil: Dubin, Marta. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
Naphthoquinones
Redox Cycle
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:11336/79881
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79881
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network_name_str CONICET Digital (CONICET)
spelling Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver PreparationsFernandez Villamil, Silvia HebeStoppani, Andrés O. M.Dubin, MartaNaphthoquinonesRedox Cyclehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The lipophilic o-naphthoquinones beta-lapachone and structural analogous quinones (CG quinones) are proposed as cytostatic, trypanocidal and antiviral agents. With rat liver microsomal NAD(P)H cytochrome P450 reductase or cytosol flavoenzyme DTD, these quinones constitute redox systems that in the presence of oxygen generate ROS. o-Naphthoquinones redox cycling, catalyzed by the NADPH cytochrome P450 reductase, generate in microsomal liver preparations: (a) semiquinone free radicals, (b) ROS and (c) inhibition of cytochrome P450-dependent reactions, exerting cytotoxic effects. Hydroquinones, are the immediate products of quinones reduction by the DTD-dependent systems. Three types of hydroquinones formed by that reaction have been proposed by Cadenas: (a) redox stable hydroquinones; (b) redox labile hydroquinones that subsequently reoxidize, with formation of semiquinone and ROS and (c) redox-labile semiquinones that immediately rearrange to potent electrophils undergoing biological alkylating reactions. Our observations with beta-lapachone and related o-naphthoquinones indicate that the corresponding hydroquinones must be included in the second group in agreement with (a) the semiquinone spectrum, demonstrated by ESR spectroscopy; (b) semiquinone (or quinone) production demonstrated by optical spectroscopy and; (c) the effect of dicoumarol on the quinone redox-cycling and oxygen consumption by the NADPH/o-naphthoquinone/DTD system. These reactions associated to DTD activity seem to rule out the contention proposing DTD as an antioxidant enzyme protecting against quinone toxicity.Fil: Fernandez Villamil, Silvia Hebe. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stoppani, Andrés O. M.. Universidad de Buenos Aires; ArgentinaFil: Dubin, Marta. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaElsevier Academic Press Inc2004-12info: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/11336/79881Fernandez Villamil, Silvia Hebe; Stoppani, Andrés O. M.; Dubin, Marta; Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations; Elsevier Academic Press Inc; Methods In Enzymology.; 378; 12-2004; 67-870076-6879CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0076-6879(04)78004-0info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0076687904780040info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:08:31Zoai:ri.conicet.gov.ar:11336/79881instacron: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 15:08:31.76CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
title Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
spellingShingle Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
Fernandez Villamil, Silvia Hebe
Naphthoquinones
Redox Cycle
title_short Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
title_full Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
title_fullStr Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
title_full_unstemmed Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
title_sort Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations
dc.creator.none.fl_str_mv Fernandez Villamil, Silvia Hebe
Stoppani, Andrés O. M.
Dubin, Marta
author Fernandez Villamil, Silvia Hebe
author_facet Fernandez Villamil, Silvia Hebe
Stoppani, Andrés O. M.
Dubin, Marta
author_role author
author2 Stoppani, Andrés O. M.
Dubin, Marta
author2_role author
author
dc.subject.none.fl_str_mv Naphthoquinones
Redox Cycle
topic Naphthoquinones
Redox Cycle
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The lipophilic o-naphthoquinones beta-lapachone and structural analogous quinones (CG quinones) are proposed as cytostatic, trypanocidal and antiviral agents. With rat liver microsomal NAD(P)H cytochrome P450 reductase or cytosol flavoenzyme DTD, these quinones constitute redox systems that in the presence of oxygen generate ROS. o-Naphthoquinones redox cycling, catalyzed by the NADPH cytochrome P450 reductase, generate in microsomal liver preparations: (a) semiquinone free radicals, (b) ROS and (c) inhibition of cytochrome P450-dependent reactions, exerting cytotoxic effects. Hydroquinones, are the immediate products of quinones reduction by the DTD-dependent systems. Three types of hydroquinones formed by that reaction have been proposed by Cadenas: (a) redox stable hydroquinones; (b) redox labile hydroquinones that subsequently reoxidize, with formation of semiquinone and ROS and (c) redox-labile semiquinones that immediately rearrange to potent electrophils undergoing biological alkylating reactions. Our observations with beta-lapachone and related o-naphthoquinones indicate that the corresponding hydroquinones must be included in the second group in agreement with (a) the semiquinone spectrum, demonstrated by ESR spectroscopy; (b) semiquinone (or quinone) production demonstrated by optical spectroscopy and; (c) the effect of dicoumarol on the quinone redox-cycling and oxygen consumption by the NADPH/o-naphthoquinone/DTD system. These reactions associated to DTD activity seem to rule out the contention proposing DTD as an antioxidant enzyme protecting against quinone toxicity.
Fil: Fernandez Villamil, Silvia Hebe. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Stoppani, Andrés O. M.. Universidad de Buenos Aires; Argentina
Fil: Dubin, Marta. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description The lipophilic o-naphthoquinones beta-lapachone and structural analogous quinones (CG quinones) are proposed as cytostatic, trypanocidal and antiviral agents. With rat liver microsomal NAD(P)H cytochrome P450 reductase or cytosol flavoenzyme DTD, these quinones constitute redox systems that in the presence of oxygen generate ROS. o-Naphthoquinones redox cycling, catalyzed by the NADPH cytochrome P450 reductase, generate in microsomal liver preparations: (a) semiquinone free radicals, (b) ROS and (c) inhibition of cytochrome P450-dependent reactions, exerting cytotoxic effects. Hydroquinones, are the immediate products of quinones reduction by the DTD-dependent systems. Three types of hydroquinones formed by that reaction have been proposed by Cadenas: (a) redox stable hydroquinones; (b) redox labile hydroquinones that subsequently reoxidize, with formation of semiquinone and ROS and (c) redox-labile semiquinones that immediately rearrange to potent electrophils undergoing biological alkylating reactions. Our observations with beta-lapachone and related o-naphthoquinones indicate that the corresponding hydroquinones must be included in the second group in agreement with (a) the semiquinone spectrum, demonstrated by ESR spectroscopy; (b) semiquinone (or quinone) production demonstrated by optical spectroscopy and; (c) the effect of dicoumarol on the quinone redox-cycling and oxygen consumption by the NADPH/o-naphthoquinone/DTD system. These reactions associated to DTD activity seem to rule out the contention proposing DTD as an antioxidant enzyme protecting against quinone toxicity.
publishDate 2004
dc.date.none.fl_str_mv 2004-12
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/11336/79881
Fernandez Villamil, Silvia Hebe; Stoppani, Andrés O. M.; Dubin, Marta; Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations; Elsevier Academic Press Inc; Methods In Enzymology.; 378; 12-2004; 67-87
0076-6879
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79881
identifier_str_mv Fernandez Villamil, Silvia Hebe; Stoppani, Andrés O. M.; Dubin, Marta; Redox Cycling of β-Lapachone and Structural Analogues in Microsomal and Cytosol Liver Preparations; Elsevier Academic Press Inc; Methods In Enzymology.; 378; 12-2004; 67-87
0076-6879
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/S0076-6879(04)78004-0
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0076687904780040
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 Elsevier Academic Press Inc
publisher.none.fl_str_mv Elsevier Academic Press 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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