Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice

Autores
de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; Larripa, Irene Beatriz
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this study we evaluated the antigenotoxic and cytoprotective capabilities of WR-2721 [S-2-(3aminopropylamino)-ethylphosphorothioic acid (amifostine)] in different normal tissues of BALB/c mice treated with idarubicin [4-demethoxydaunorubicin (IDA)]. The aminothiol WR-2721 is a pro-drug that requires dephosphorylation to its active metabolite WR-1065, to produce selectively cytoprotective activity in normal tissues exposed to radio- and chemotherapeutic agents, without protecting malignant tissues. IDA is an effective chemotherapeutic agent against hematological diseases, but produces a broad spectrum of toxicity in nontumoral cells. Animals were injected intravenously with WR-2721 (250 mg/kg) or IDA (6 mg/kg) and WR-2721/IDA. Micronuclei frequency in bone marraw was measured 24 and 48 hr after initiation of the treatments. The IDA-treated group showed increased levels of micronuclei. However, the WR-2721- and WR-2721/IDA-treated groups did not show differences from the controls. Genetic damage was evaluated by alkaline single-cell gel electrophoresis at 24-hr posttreatments. Important DNA damage was observed in liver, spleen, and peripheral blood cells of mice treated with IDA. The presence of WR-2721 diminished that damaging effect only in liver cells. The apoptotic index was measured in liver and spleen tissues by the TUNEL assay 14 and 24 hr after treatment. In liver we observed an increased percentage of apoptotic cells at 24 hr for the IDA-treated group, whereas the WR-2721 and WR-2721/IDA groups remained at low levels. Splenic cells treated with IDA and WR-2721/IDA showed increased DNA fragmentation levels at any time. In conclusion, WR-2721 has a tissue-specific antigenotoxic and cytoprotective effect in IDA-treated mice using these experimental conditions.
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Materia
Amifostine
Apoptosis
Cytoprotection
Dna Damage
Dna Topoisomerase Ii
Idarubicin
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:11336/55113
Acceder
id CONICETDig_f79fef81e4b792bcb4a253b9575de735
oai_identifier_str oai:ri.conicet.gov.ar:11336/55113
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated micede Campos Nebel, Ildefonso MarceloGonzalez Cid, Marcela BeatrizLarripa, Irene BeatrizAmifostineApoptosisCytoprotectionDna DamageDna Topoisomerase IiIdarubicinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In this study we evaluated the antigenotoxic and cytoprotective capabilities of WR-2721 [S-2-(3aminopropylamino)-ethylphosphorothioic acid (amifostine)] in different normal tissues of BALB/c mice treated with idarubicin [4-demethoxydaunorubicin (IDA)]. The aminothiol WR-2721 is a pro-drug that requires dephosphorylation to its active metabolite WR-1065, to produce selectively cytoprotective activity in normal tissues exposed to radio- and chemotherapeutic agents, without protecting malignant tissues. IDA is an effective chemotherapeutic agent against hematological diseases, but produces a broad spectrum of toxicity in nontumoral cells. Animals were injected intravenously with WR-2721 (250 mg/kg) or IDA (6 mg/kg) and WR-2721/IDA. Micronuclei frequency in bone marraw was measured 24 and 48 hr after initiation of the treatments. The IDA-treated group showed increased levels of micronuclei. However, the WR-2721- and WR-2721/IDA-treated groups did not show differences from the controls. Genetic damage was evaluated by alkaline single-cell gel electrophoresis at 24-hr posttreatments. Important DNA damage was observed in liver, spleen, and peripheral blood cells of mice treated with IDA. The presence of WR-2721 diminished that damaging effect only in liver cells. The apoptotic index was measured in liver and spleen tissues by the TUNEL assay 14 and 24 hr after treatment. In liver we observed an increased percentage of apoptotic cells at 24 hr for the IDA-treated group, whereas the WR-2721 and WR-2721/IDA groups remained at low levels. Splenic cells treated with IDA and WR-2721/IDA showed increased DNA fragmentation levels at any time. In conclusion, WR-2721 has a tissue-specific antigenotoxic and cytoprotective effect in IDA-treated mice using these experimental conditions.Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaWiley-liss, Inc2002-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55113de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; Larripa, Irene Beatriz; Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice; Wiley-liss, Inc; Environmental And Molecular Mutagenesis; 39; 1; 12-2002; 3-90893-66921098-2280CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/em.1081info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/em.1081info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:53:31Zoai:ri.conicet.gov.ar:11336/55113instacron: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 09:53:31.494CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
title Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
spellingShingle Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
de Campos Nebel, Ildefonso Marcelo
Amifostine
Apoptosis
Cytoprotection
Dna Damage
Dna Topoisomerase Ii
Idarubicin
title_short Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
title_full Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
title_fullStr Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
title_full_unstemmed Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
title_sort Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice
dc.creator.none.fl_str_mv de Campos Nebel, Ildefonso Marcelo
Gonzalez Cid, Marcela Beatriz
Larripa, Irene Beatriz
author de Campos Nebel, Ildefonso Marcelo
author_facet de Campos Nebel, Ildefonso Marcelo
Gonzalez Cid, Marcela Beatriz
Larripa, Irene Beatriz
author_role author
author2 Gonzalez Cid, Marcela Beatriz
Larripa, Irene Beatriz
author2_role author
author
dc.subject.none.fl_str_mv Amifostine
Apoptosis
Cytoprotection
Dna Damage
Dna Topoisomerase Ii
Idarubicin
topic Amifostine
Apoptosis
Cytoprotection
Dna Damage
Dna Topoisomerase Ii
Idarubicin
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 this study we evaluated the antigenotoxic and cytoprotective capabilities of WR-2721 [S-2-(3aminopropylamino)-ethylphosphorothioic acid (amifostine)] in different normal tissues of BALB/c mice treated with idarubicin [4-demethoxydaunorubicin (IDA)]. The aminothiol WR-2721 is a pro-drug that requires dephosphorylation to its active metabolite WR-1065, to produce selectively cytoprotective activity in normal tissues exposed to radio- and chemotherapeutic agents, without protecting malignant tissues. IDA is an effective chemotherapeutic agent against hematological diseases, but produces a broad spectrum of toxicity in nontumoral cells. Animals were injected intravenously with WR-2721 (250 mg/kg) or IDA (6 mg/kg) and WR-2721/IDA. Micronuclei frequency in bone marraw was measured 24 and 48 hr after initiation of the treatments. The IDA-treated group showed increased levels of micronuclei. However, the WR-2721- and WR-2721/IDA-treated groups did not show differences from the controls. Genetic damage was evaluated by alkaline single-cell gel electrophoresis at 24-hr posttreatments. Important DNA damage was observed in liver, spleen, and peripheral blood cells of mice treated with IDA. The presence of WR-2721 diminished that damaging effect only in liver cells. The apoptotic index was measured in liver and spleen tissues by the TUNEL assay 14 and 24 hr after treatment. In liver we observed an increased percentage of apoptotic cells at 24 hr for the IDA-treated group, whereas the WR-2721 and WR-2721/IDA groups remained at low levels. Splenic cells treated with IDA and WR-2721/IDA showed increased DNA fragmentation levels at any time. In conclusion, WR-2721 has a tissue-specific antigenotoxic and cytoprotective effect in IDA-treated mice using these experimental conditions.
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
description In this study we evaluated the antigenotoxic and cytoprotective capabilities of WR-2721 [S-2-(3aminopropylamino)-ethylphosphorothioic acid (amifostine)] in different normal tissues of BALB/c mice treated with idarubicin [4-demethoxydaunorubicin (IDA)]. The aminothiol WR-2721 is a pro-drug that requires dephosphorylation to its active metabolite WR-1065, to produce selectively cytoprotective activity in normal tissues exposed to radio- and chemotherapeutic agents, without protecting malignant tissues. IDA is an effective chemotherapeutic agent against hematological diseases, but produces a broad spectrum of toxicity in nontumoral cells. Animals were injected intravenously with WR-2721 (250 mg/kg) or IDA (6 mg/kg) and WR-2721/IDA. Micronuclei frequency in bone marraw was measured 24 and 48 hr after initiation of the treatments. The IDA-treated group showed increased levels of micronuclei. However, the WR-2721- and WR-2721/IDA-treated groups did not show differences from the controls. Genetic damage was evaluated by alkaline single-cell gel electrophoresis at 24-hr posttreatments. Important DNA damage was observed in liver, spleen, and peripheral blood cells of mice treated with IDA. The presence of WR-2721 diminished that damaging effect only in liver cells. The apoptotic index was measured in liver and spleen tissues by the TUNEL assay 14 and 24 hr after treatment. In liver we observed an increased percentage of apoptotic cells at 24 hr for the IDA-treated group, whereas the WR-2721 and WR-2721/IDA groups remained at low levels. Splenic cells treated with IDA and WR-2721/IDA showed increased DNA fragmentation levels at any time. In conclusion, WR-2721 has a tissue-specific antigenotoxic and cytoprotective effect in IDA-treated mice using these experimental conditions.
publishDate 2002
dc.date.none.fl_str_mv 2002-12
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/11336/55113
de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; Larripa, Irene Beatriz; Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice; Wiley-liss, Inc; Environmental And Molecular Mutagenesis; 39; 1; 12-2002; 3-9
0893-6692
1098-2280
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55113
identifier_str_mv de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; Larripa, Irene Beatriz; Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice; Wiley-liss, Inc; Environmental And Molecular Mutagenesis; 39; 1; 12-2002; 3-9
0893-6692
1098-2280
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/em.1081
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/em.1081
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
dc.publisher.none.fl_str_mv Wiley-liss, Inc
publisher.none.fl_str_mv Wiley-liss, 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 13.070432

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