Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)

Autores
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Angerosa, M.; Rivero, M.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional ´in vitro´ studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.
Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cao, Gabriel Fernando. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Angerosa, M.. Hospital Aleman; Argentina
Fil: Rivero, M.. Hospital Aleman; Argentina
Materia
Phosphodiesterase 5 Inhibitor
Zucker Diabetic Fatty Rat
Heat-Shock Proteins
Cavernous Tissue
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:11336/41756
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/41756
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)Toblli, Jorge EduardoCao, Gabriel FernandoAngerosa, M.Rivero, M.Phosphodiesterase 5 InhibitorZucker Diabetic Fatty RatHeat-Shock ProteinsCavernous Tissuehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional ´in vitro´ studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cao, Gabriel Fernando. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Angerosa, M.. Hospital Aleman; ArgentinaFil: Rivero, M.. Hospital Aleman; ArgentinaNature Publishing Group2015-09info: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/11336/41756Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Angerosa, M.; Rivero, M.; Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa); Nature Publishing Group; International Journal Of Impotence Research : Official Journal Of The International Society For Impotence Research.; 27; 5; 9-2015; 182-1900955-9930CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/ijir.2015.13info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ijir201513info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:25Zoai:ri.conicet.gov.ar:11336/41756instacron: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 09:58:26.079CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
title Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
spellingShingle Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
Toblli, Jorge Eduardo
Phosphodiesterase 5 Inhibitor
Zucker Diabetic Fatty Rat
Heat-Shock Proteins
Cavernous Tissue
title_short Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
title_full Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
title_fullStr Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
title_full_unstemmed Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
title_sort Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa)
dc.creator.none.fl_str_mv Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Angerosa, M.
Rivero, M.
author Toblli, Jorge Eduardo
author_facet Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Angerosa, M.
Rivero, M.
author_role author
author2 Cao, Gabriel Fernando
Angerosa, M.
Rivero, M.
author2_role author
author
author
dc.subject.none.fl_str_mv Phosphodiesterase 5 Inhibitor
Zucker Diabetic Fatty Rat
Heat-Shock Proteins
Cavernous Tissue
topic Phosphodiesterase 5 Inhibitor
Zucker Diabetic Fatty Rat
Heat-Shock Proteins
Cavernous Tissue
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional ´in vitro´ studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.
Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cao, Gabriel Fernando. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Angerosa, M.. Hospital Aleman; Argentina
Fil: Rivero, M.. Hospital Aleman; Argentina
description Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional ´in vitro´ studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.
publishDate 2015
dc.date.none.fl_str_mv 2015-09
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/11336/41756
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Angerosa, M.; Rivero, M.; Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa); Nature Publishing Group; International Journal Of Impotence Research : Official Journal Of The International Society For Impotence Research.; 27; 5; 9-2015; 182-190
0955-9930
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41756
identifier_str_mv Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Angerosa, M.; Rivero, M.; Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF/fa/fa); Nature Publishing Group; International Journal Of Impotence Research : Official Journal Of The International Society For Impotence Research.; 27; 5; 9-2015; 182-190
0955-9930
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/ijir.2015.13
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ijir201513
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 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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