Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model

Autores
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Oliveri, Leda María; Angerosa, Margarita
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Oliveri, Leda María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Materia
Intravenous iron
Iron dextran
Iron isomaltoside 1000
Oxidative stress
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:11336/239801
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/239801
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical modelToblli, Jorge EduardoCao, Gabriel FernandoOliveri, Leda MaríaAngerosa, MargaritaIntravenous ironIron dextranIron isomaltoside 1000Oxidative stresshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Oliveri, Leda María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaEcv-editio Cantor Verlag Medizin Naturwissenschaften2012-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/239801Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Oliveri, Leda María; Angerosa, Margarita; Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model; Ecv-editio Cantor Verlag Medizin Naturwissenschaften; Arzneimittel Forschung Drug Research; 61; 10; 2-2012; 553-5650004-4172CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0031-1300553info:eu-repo/semantics/altIdentifier/doi/10.1055/s-0031-1300553info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:45Zoai:ri.conicet.gov.ar:11336/239801instacron: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 10:02:45.299CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
title Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
spellingShingle Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
Toblli, Jorge Eduardo
Intravenous iron
Iron dextran
Iron isomaltoside 1000
Oxidative stress
title_short Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
title_full Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
title_fullStr Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
title_full_unstemmed Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
title_sort Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model
dc.creator.none.fl_str_mv Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Oliveri, Leda María
Angerosa, Margarita
author Toblli, Jorge Eduardo
author_facet Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Oliveri, Leda María
Angerosa, Margarita
author_role author
author2 Cao, Gabriel Fernando
Oliveri, Leda María
Angerosa, Margarita
author2_role author
author
author
dc.subject.none.fl_str_mv Intravenous iron
Iron dextran
Iron isomaltoside 1000
Oxidative stress
topic Intravenous iron
Iron dextran
Iron isomaltoside 1000
Oxidative stress
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Oliveri, Leda María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
description The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.
publishDate 2012
dc.date.none.fl_str_mv 2012-02
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/11336/239801
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Oliveri, Leda María; Angerosa, Margarita; Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model; Ecv-editio Cantor Verlag Medizin Naturwissenschaften; Arzneimittel Forschung Drug Research; 61; 10; 2-2012; 553-565
0004-4172
CONICET Digital
CONICET
url http://hdl.handle.net/11336/239801
identifier_str_mv Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Oliveri, Leda María; Angerosa, Margarita; Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model; Ecv-editio Cantor Verlag Medizin Naturwissenschaften; Arzneimittel Forschung Drug Research; 61; 10; 2-2012; 553-565
0004-4172
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.thieme-connect.de/products/ejournals/abstract/10.1055/s-0031-1300553
info:eu-repo/semantics/altIdentifier/doi/10.1055/s-0031-1300553
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 Ecv-editio Cantor Verlag Medizin Naturwissenschaften
publisher.none.fl_str_mv Ecv-editio Cantor Verlag Medizin Naturwissenschaften
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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