Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats

Autores
Giani, Jorge Fernando; Burghi, Valeria; Veiras, Luciana Cecilia; Tomat, Analia Lorena; Muñoz, Marina Cecilia; Cao, Gabriel Fernando; Turyn, Daniel; Toblli, Jorge Eduardo; Dominici, Fernando Pablo
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Angiotensin (Ang)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus, in the current study we evaluated the renal effects of a chronic Ang-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen week-old male ZDF and their respective controls (Lean Zucker rats; LZR) were used for this study. The protocol involved three groups: 1) LZR+saline; 2) ZDF+saline; and 3) ZDF+Ang-(1-7). For 2 weeks, animals were implanted with subcutaneous osmotic pumps that delivered either saline or Ang-(1-7) (100 ng⋅kg(-1)⋅min(-1)) (n=4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ED-1, hypoxia-inducible factor-1α (HIF-1α) and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. Ang-(1-7) induced a reduction in triglyceridemia, proteinuria and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, Ang-(1-7) reduced renal fibrosis, decreased thiobarbituric acid reactive substances and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-α, ED-1, HIF-1α and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and Ang II levels remained unchanged after treatment with Ang-(1-7). Chronic Ang-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress and inflammatory markers. Thus, Ang-(1-7) emerges as a novel target for treatment of diabetic nephropathy.
Fil: Giani, Jorge Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Burghi, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Veiras, Luciana Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Tomat, Analia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Muñoz, Marina Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina
Fil: Turyn, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Materia
INSULIN
ANGIOTENSIN
DIABETES
KIDNEY
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:11336/243221
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty RatsGiani, Jorge FernandoBurghi, ValeriaVeiras, Luciana CeciliaTomat, Analia LorenaMuñoz, Marina CeciliaCao, Gabriel FernandoTuryn, DanielToblli, Jorge EduardoDominici, Fernando PabloINSULINANGIOTENSINDIABETESKIDNEYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Angiotensin (Ang)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus, in the current study we evaluated the renal effects of a chronic Ang-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen week-old male ZDF and their respective controls (Lean Zucker rats; LZR) were used for this study. The protocol involved three groups: 1) LZR+saline; 2) ZDF+saline; and 3) ZDF+Ang-(1-7). For 2 weeks, animals were implanted with subcutaneous osmotic pumps that delivered either saline or Ang-(1-7) (100 ng⋅kg(-1)⋅min(-1)) (n=4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ED-1, hypoxia-inducible factor-1α (HIF-1α) and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. Ang-(1-7) induced a reduction in triglyceridemia, proteinuria and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, Ang-(1-7) reduced renal fibrosis, decreased thiobarbituric acid reactive substances and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-α, ED-1, HIF-1α and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and Ang II levels remained unchanged after treatment with Ang-(1-7). Chronic Ang-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress and inflammatory markers. Thus, Ang-(1-7) emerges as a novel target for treatment of diabetic nephropathy.Fil: Giani, Jorge Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Burghi, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Veiras, Luciana Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Tomat, Analia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Muñoz, Marina Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; ArgentinaFil: Turyn, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; ArgentinaFil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaAmerican Physiological Society2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/243221Giani, Jorge Fernando; Burghi, Valeria; Veiras, Luciana Cecilia; Tomat, Analia Lorena; Muñoz, Marina Cecilia; et al.; Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-2012; F1606-F16151931-857XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajprenal.00063.2012info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00063.2012info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:37Zoai:ri.conicet.gov.ar:11336/243221instacron: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 09:59:37.436CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
title Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
spellingShingle Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
Giani, Jorge Fernando
INSULIN
ANGIOTENSIN
DIABETES
KIDNEY
title_short Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
title_full Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
title_fullStr Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
title_full_unstemmed Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
title_sort Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
dc.creator.none.fl_str_mv Giani, Jorge Fernando
Burghi, Valeria
Veiras, Luciana Cecilia
Tomat, Analia Lorena
Muñoz, Marina Cecilia
Cao, Gabriel Fernando
Turyn, Daniel
Toblli, Jorge Eduardo
Dominici, Fernando Pablo
author Giani, Jorge Fernando
author_facet Giani, Jorge Fernando
Burghi, Valeria
Veiras, Luciana Cecilia
Tomat, Analia Lorena
Muñoz, Marina Cecilia
Cao, Gabriel Fernando
Turyn, Daniel
Toblli, Jorge Eduardo
Dominici, Fernando Pablo
author_role author
author2 Burghi, Valeria
Veiras, Luciana Cecilia
Tomat, Analia Lorena
Muñoz, Marina Cecilia
Cao, Gabriel Fernando
Turyn, Daniel
Toblli, Jorge Eduardo
Dominici, Fernando Pablo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv INSULIN
ANGIOTENSIN
DIABETES
KIDNEY
topic INSULIN
ANGIOTENSIN
DIABETES
KIDNEY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Angiotensin (Ang)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus, in the current study we evaluated the renal effects of a chronic Ang-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen week-old male ZDF and their respective controls (Lean Zucker rats; LZR) were used for this study. The protocol involved three groups: 1) LZR+saline; 2) ZDF+saline; and 3) ZDF+Ang-(1-7). For 2 weeks, animals were implanted with subcutaneous osmotic pumps that delivered either saline or Ang-(1-7) (100 ng⋅kg(-1)⋅min(-1)) (n=4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ED-1, hypoxia-inducible factor-1α (HIF-1α) and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. Ang-(1-7) induced a reduction in triglyceridemia, proteinuria and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, Ang-(1-7) reduced renal fibrosis, decreased thiobarbituric acid reactive substances and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-α, ED-1, HIF-1α and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and Ang II levels remained unchanged after treatment with Ang-(1-7). Chronic Ang-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress and inflammatory markers. Thus, Ang-(1-7) emerges as a novel target for treatment of diabetic nephropathy.
Fil: Giani, Jorge Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Burghi, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Veiras, Luciana Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Tomat, Analia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Muñoz, Marina Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina
Fil: Turyn, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
description Angiotensin (Ang)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus, in the current study we evaluated the renal effects of a chronic Ang-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen week-old male ZDF and their respective controls (Lean Zucker rats; LZR) were used for this study. The protocol involved three groups: 1) LZR+saline; 2) ZDF+saline; and 3) ZDF+Ang-(1-7). For 2 weeks, animals were implanted with subcutaneous osmotic pumps that delivered either saline or Ang-(1-7) (100 ng⋅kg(-1)⋅min(-1)) (n=4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ED-1, hypoxia-inducible factor-1α (HIF-1α) and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. Ang-(1-7) induced a reduction in triglyceridemia, proteinuria and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, Ang-(1-7) reduced renal fibrosis, decreased thiobarbituric acid reactive substances and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-α, ED-1, HIF-1α and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and Ang II levels remained unchanged after treatment with Ang-(1-7). Chronic Ang-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress and inflammatory markers. Thus, Ang-(1-7) emerges as a novel target for treatment of diabetic nephropathy.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/243221
Giani, Jorge Fernando; Burghi, Valeria; Veiras, Luciana Cecilia; Tomat, Analia Lorena; Muñoz, Marina Cecilia; et al.; Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-2012; F1606-F1615
1931-857X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243221
identifier_str_mv Giani, Jorge Fernando; Burghi, Valeria; Veiras, Luciana Cecilia; Tomat, Analia Lorena; Muñoz, Marina Cecilia; et al.; Angiotensin-(1-7) Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-2012; F1606-F1615
1931-857X
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://journals.physiology.org/doi/full/10.1152/ajprenal.00063.2012
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00063.2012
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
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dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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