Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome

Autores
Dran, Graciela Isabel; Fernández, Gabriela Cristina; Rubel, Carolina J.; Bermejo, Emilse; Gómez, Sonia Alejandra; Meiss, Roberto Pablo; Isturiz, Martín Amadeo; Palermo, Marina Sandra
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background : Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified. Methods : A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of L-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody. Results : Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of L-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion. Conclusions : NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.
Fil: Dran, Graciela Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rubel, Carolina J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bermejo, Emilse. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gómez, Sonia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Meiss, Roberto Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Nitric Oxide
Shiga Toxin
Hus
Mice
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:11336/55334
Acceder
id CONICETDig_c6be043fd75568723222d6cc60d98217
oai_identifier_str oai:ri.conicet.gov.ar:11336/55334
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndromeDran, Graciela IsabelFernández, Gabriela CristinaRubel, Carolina J.Bermejo, EmilseGómez, Sonia AlejandraMeiss, Roberto PabloIsturiz, Martín AmadeoPalermo, Marina SandraNitric OxideShiga ToxinHusMicehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background : Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified. Methods : A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of L-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody. Results : Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of L-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion. Conclusions : NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.Fil: Dran, Graciela Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rubel, Carolina J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bermejo, Emilse. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gómez, Sonia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Meiss, Roberto Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaNature Publishing Group2002-10info: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/11336/55334Dran, Graciela Isabel; Fernández, Gabriela Cristina; Rubel, Carolina J.; Bermejo, Emilse; Gómez, Sonia Alejandra; et al.; Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome; Nature Publishing Group; Kidney International; 62; 4; 10-2002; 1338-13480085-2538CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1523-1755.2002.kid554.xinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0085253815486764info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:51Zoai:ri.conicet.gov.ar:11336/55334instacron: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 10:08:51.857CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
title Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
spellingShingle Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
Dran, Graciela Isabel
Nitric Oxide
Shiga Toxin
Hus
Mice
title_short Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
title_full Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
title_fullStr Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
title_full_unstemmed Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
title_sort Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome
dc.creator.none.fl_str_mv Dran, Graciela Isabel
Fernández, Gabriela Cristina
Rubel, Carolina J.
Bermejo, Emilse
Gómez, Sonia Alejandra
Meiss, Roberto Pablo
Isturiz, Martín Amadeo
Palermo, Marina Sandra
author Dran, Graciela Isabel
author_facet Dran, Graciela Isabel
Fernández, Gabriela Cristina
Rubel, Carolina J.
Bermejo, Emilse
Gómez, Sonia Alejandra
Meiss, Roberto Pablo
Isturiz, Martín Amadeo
Palermo, Marina Sandra
author_role author
author2 Fernández, Gabriela Cristina
Rubel, Carolina J.
Bermejo, Emilse
Gómez, Sonia Alejandra
Meiss, Roberto Pablo
Isturiz, Martín Amadeo
Palermo, Marina Sandra
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nitric Oxide
Shiga Toxin
Hus
Mice
topic Nitric Oxide
Shiga Toxin
Hus
Mice
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background : Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified. Methods : A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of L-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody. Results : Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of L-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion. Conclusions : NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.
Fil: Dran, Graciela Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rubel, Carolina J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bermejo, Emilse. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gómez, Sonia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Meiss, Roberto Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Background : Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified. Methods : A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of L-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody. Results : Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of L-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion. Conclusions : NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.
publishDate 2002
dc.date.none.fl_str_mv 2002-10
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/11336/55334
Dran, Graciela Isabel; Fernández, Gabriela Cristina; Rubel, Carolina J.; Bermejo, Emilse; Gómez, Sonia Alejandra; et al.; Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome; Nature Publishing Group; Kidney International; 62; 4; 10-2002; 1338-1348
0085-2538
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55334
identifier_str_mv Dran, Graciela Isabel; Fernández, Gabriela Cristina; Rubel, Carolina J.; Bermejo, Emilse; Gómez, Sonia Alejandra; et al.; Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome; Nature Publishing Group; Kidney International; 62; 4; 10-2002; 1338-1348
0085-2538
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1523-1755.2002.kid554.x
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0085253815486764
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 13.13397

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