Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems
- Autores
- Montalto, Maria; Diaz, Edith Graciela; Castro, Jose Alberto
- Año de publicación
- 2002
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Liver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity.
Fil: Montalto, Maria. 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
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina - Materia
-
Liver Nuclei or Microsomes or Mitochondria
Nifurtimox
Nitric Oxide And Peroxynitrite Formation
Nitroreductase Activity - 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:11336/82223
Ver los metadatos del registro completo
id |
CONICETDig_427e0ccb7dafc32bffed324c955193d8 |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/82223 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
network_name_str |
CONICET Digital (CONICET) |
spelling |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systemsMontalto, MariaDiaz, Edith GracielaCastro, Jose AlbertoLiver Nuclei or Microsomes or MitochondriaNifurtimoxNitric Oxide And Peroxynitrite FormationNitroreductase Activityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Liver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity.Fil: Montalto, Maria. 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); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaElsevier Ireland2002-11info: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/11336/82223Montalto, Maria; Diaz, Edith Graciela; Castro, Jose Alberto; Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems; Elsevier Ireland; Toxicology Letters; 136; 1; 11-2002; 1-80378-4274CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0378427402002382info:eu-repo/semantics/altIdentifier/doi/10.1016/S0378-4274(02)00238-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:09Zoai:ri.conicet.gov.ar:11336/82223instacron: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 10:07:09.83CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
title |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
spellingShingle |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems Montalto, Maria Liver Nuclei or Microsomes or Mitochondria Nifurtimox Nitric Oxide And Peroxynitrite Formation Nitroreductase Activity |
title_short |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
title_full |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
title_fullStr |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
title_full_unstemmed |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
title_sort |
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems |
dc.creator.none.fl_str_mv |
Montalto, Maria Diaz, Edith Graciela Castro, Jose Alberto |
author |
Montalto, Maria |
author_facet |
Montalto, Maria Diaz, Edith Graciela Castro, Jose Alberto |
author_role |
author |
author2 |
Diaz, Edith Graciela Castro, Jose Alberto |
author2_role |
author author |
dc.subject.none.fl_str_mv |
Liver Nuclei or Microsomes or Mitochondria Nifurtimox Nitric Oxide And Peroxynitrite Formation Nitroreductase Activity |
topic |
Liver Nuclei or Microsomes or Mitochondria Nifurtimox Nitric Oxide And Peroxynitrite Formation Nitroreductase Activity |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Liver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity. Fil: Montalto, Maria. 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 Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina |
description |
Liver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-11 |
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/11336/82223 Montalto, Maria; Diaz, Edith Graciela; Castro, Jose Alberto; Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems; Elsevier Ireland; Toxicology Letters; 136; 1; 11-2002; 1-8 0378-4274 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/82223 |
identifier_str_mv |
Montalto, Maria; Diaz, Edith Graciela; Castro, Jose Alberto; Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems; Elsevier Ireland; Toxicology Letters; 136; 1; 11-2002; 1-8 0378-4274 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.sciencedirect.com/science/article/pii/S0378427402002382 info:eu-repo/semantics/altIdentifier/doi/10.1016/S0378-4274(02)00238-2 |
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 |
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 |
_version_ |
1842269991839203328 |
score |
13.13397 |