Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion

Autores
Jarazo Dietrich, Sabrina Soledad; Fass, Mónica Irina; Jacobo, Patricia Verónica; Sobarzo, Cristian Marcelo Alejandro; Lustig, Livia; Theas, Maria Susana
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Although the testis is considered an immunoprivileged organ it can orchestrate immune responses against pathological insults such as infection and trauma. Experimental autoimmune orchitis (EAO) is a model of chronic inflammation whose main histopathological features it shares with human orchitis. In EAO an increased number of macrophages infiltrate the interstitium concomitantly with progressive germ cell degeneration and impaired steroidogenesis. Up-regulation of nitric oxide (NO)-NO synthase (NOS) system occurs, macrophages being the main producers of NO. Objective: The aim of our study was to evaluate the role of NO-NOS system in orchitis development and determine the involvement of NO released by testicular macrophages on germ cell apoptosis and testosterone secretion. Method and Results: EAO was induced in rats by immunization with testicular homogenate and adjuvants (E group) and a group of untreated normal rats (N) was also studied. Blockage of NOS by i.p. injection of E rats with a competitive inhibitor of NOS, L-NAME (8mg/kg), significantly reduced the incidence and severity of orchitis and lowered testicular nitrite content. L-NAME reduced germ cell apoptosis and restored intratesticular testosterone levels, without variations in serum LH. Co-culture of N testicular fragments with testicular macrophages obtained from EAO rats significantly increased germ cell apoptosis and testosterone secretion, whereas addition of L-NAME lowered both effects and reduced nitrite content. Incubation of testicular fragments from N rats with a NO donor DETA-NOnoate (DETA-NO) induced germ cell apoptosis through external and internal apoptotic pathways, an effect prevented by N-acetyl-L-cysteine (NAC). DETA-NO inhibited testosterone released from Leydig cells, whereas NAC (from 2.5 to 15 mM) did not prevent this effect. Conclusions: We demonstrated that NO-NOS system is involved in the impairment of testicular function in orchitis. NO secreted mainly by testicular macrophages could promote oxidative stress inducing ST damage and interfering in Leydig cell function.
Fil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Fass, Mónica Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Sobarzo, Cristian Marcelo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Materia
Autoimmune Orchitis
Testis
NOS-NO System
Testosterone
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15190
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15190
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretionJarazo Dietrich, Sabrina SoledadFass, Mónica IrinaJacobo, Patricia VerónicaSobarzo, Cristian Marcelo AlejandroLustig, LiviaTheas, Maria SusanaAutoimmune OrchitisTestisNOS-NO SystemTestosteronehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Although the testis is considered an immunoprivileged organ it can orchestrate immune responses against pathological insults such as infection and trauma. Experimental autoimmune orchitis (EAO) is a model of chronic inflammation whose main histopathological features it shares with human orchitis. In EAO an increased number of macrophages infiltrate the interstitium concomitantly with progressive germ cell degeneration and impaired steroidogenesis. Up-regulation of nitric oxide (NO)-NO synthase (NOS) system occurs, macrophages being the main producers of NO. Objective: The aim of our study was to evaluate the role of NO-NOS system in orchitis development and determine the involvement of NO released by testicular macrophages on germ cell apoptosis and testosterone secretion. Method and Results: EAO was induced in rats by immunization with testicular homogenate and adjuvants (E group) and a group of untreated normal rats (N) was also studied. Blockage of NOS by i.p. injection of E rats with a competitive inhibitor of NOS, L-NAME (8mg/kg), significantly reduced the incidence and severity of orchitis and lowered testicular nitrite content. L-NAME reduced germ cell apoptosis and restored intratesticular testosterone levels, without variations in serum LH. Co-culture of N testicular fragments with testicular macrophages obtained from EAO rats significantly increased germ cell apoptosis and testosterone secretion, whereas addition of L-NAME lowered both effects and reduced nitrite content. Incubation of testicular fragments from N rats with a NO donor DETA-NOnoate (DETA-NO) induced germ cell apoptosis through external and internal apoptotic pathways, an effect prevented by N-acetyl-L-cysteine (NAC). DETA-NO inhibited testosterone released from Leydig cells, whereas NAC (from 2.5 to 15 mM) did not prevent this effect. Conclusions: We demonstrated that NO-NOS system is involved in the impairment of testicular function in orchitis. NO secreted mainly by testicular macrophages could promote oxidative stress inducing ST damage and interfering in Leydig cell function.Fil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaFil: Fass, Mónica Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaFil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaFil: Sobarzo, Cristian Marcelo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaFil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaFil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; ArgentinaPublic Library of Science2015-06info: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/11336/15190Jarazo Dietrich, Sabrina Soledad; Fass, Mónica Irina; Jacobo, Patricia Verónica; Sobarzo, Cristian Marcelo Alejandro; Lustig, Livia; et al.; Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion; Public Library of Science; Plos One; 10; 6; 6-2015; e01287091932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128709info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0128709info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:21Zoai:ri.conicet.gov.ar:11336/15190instacron: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 09:59:21.724CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
title Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
spellingShingle Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
Jarazo Dietrich, Sabrina Soledad
Autoimmune Orchitis
Testis
NOS-NO System
Testosterone
title_short Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
title_full Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
title_fullStr Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
title_full_unstemmed Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
title_sort Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion
dc.creator.none.fl_str_mv Jarazo Dietrich, Sabrina Soledad
Fass, Mónica Irina
Jacobo, Patricia Verónica
Sobarzo, Cristian Marcelo Alejandro
Lustig, Livia
Theas, Maria Susana
author Jarazo Dietrich, Sabrina Soledad
author_facet Jarazo Dietrich, Sabrina Soledad
Fass, Mónica Irina
Jacobo, Patricia Verónica
Sobarzo, Cristian Marcelo Alejandro
Lustig, Livia
Theas, Maria Susana
author_role author
author2 Fass, Mónica Irina
Jacobo, Patricia Verónica
Sobarzo, Cristian Marcelo Alejandro
Lustig, Livia
Theas, Maria Susana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Autoimmune Orchitis
Testis
NOS-NO System
Testosterone
topic Autoimmune Orchitis
Testis
NOS-NO System
Testosterone
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Although the testis is considered an immunoprivileged organ it can orchestrate immune responses against pathological insults such as infection and trauma. Experimental autoimmune orchitis (EAO) is a model of chronic inflammation whose main histopathological features it shares with human orchitis. In EAO an increased number of macrophages infiltrate the interstitium concomitantly with progressive germ cell degeneration and impaired steroidogenesis. Up-regulation of nitric oxide (NO)-NO synthase (NOS) system occurs, macrophages being the main producers of NO. Objective: The aim of our study was to evaluate the role of NO-NOS system in orchitis development and determine the involvement of NO released by testicular macrophages on germ cell apoptosis and testosterone secretion. Method and Results: EAO was induced in rats by immunization with testicular homogenate and adjuvants (E group) and a group of untreated normal rats (N) was also studied. Blockage of NOS by i.p. injection of E rats with a competitive inhibitor of NOS, L-NAME (8mg/kg), significantly reduced the incidence and severity of orchitis and lowered testicular nitrite content. L-NAME reduced germ cell apoptosis and restored intratesticular testosterone levels, without variations in serum LH. Co-culture of N testicular fragments with testicular macrophages obtained from EAO rats significantly increased germ cell apoptosis and testosterone secretion, whereas addition of L-NAME lowered both effects and reduced nitrite content. Incubation of testicular fragments from N rats with a NO donor DETA-NOnoate (DETA-NO) induced germ cell apoptosis through external and internal apoptotic pathways, an effect prevented by N-acetyl-L-cysteine (NAC). DETA-NO inhibited testosterone released from Leydig cells, whereas NAC (from 2.5 to 15 mM) did not prevent this effect. Conclusions: We demonstrated that NO-NOS system is involved in the impairment of testicular function in orchitis. NO secreted mainly by testicular macrophages could promote oxidative stress inducing ST damage and interfering in Leydig cell function.
Fil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Fass, Mónica Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Sobarzo, Cristian Marcelo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
Fil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina
description Background: Although the testis is considered an immunoprivileged organ it can orchestrate immune responses against pathological insults such as infection and trauma. Experimental autoimmune orchitis (EAO) is a model of chronic inflammation whose main histopathological features it shares with human orchitis. In EAO an increased number of macrophages infiltrate the interstitium concomitantly with progressive germ cell degeneration and impaired steroidogenesis. Up-regulation of nitric oxide (NO)-NO synthase (NOS) system occurs, macrophages being the main producers of NO. Objective: The aim of our study was to evaluate the role of NO-NOS system in orchitis development and determine the involvement of NO released by testicular macrophages on germ cell apoptosis and testosterone secretion. Method and Results: EAO was induced in rats by immunization with testicular homogenate and adjuvants (E group) and a group of untreated normal rats (N) was also studied. Blockage of NOS by i.p. injection of E rats with a competitive inhibitor of NOS, L-NAME (8mg/kg), significantly reduced the incidence and severity of orchitis and lowered testicular nitrite content. L-NAME reduced germ cell apoptosis and restored intratesticular testosterone levels, without variations in serum LH. Co-culture of N testicular fragments with testicular macrophages obtained from EAO rats significantly increased germ cell apoptosis and testosterone secretion, whereas addition of L-NAME lowered both effects and reduced nitrite content. Incubation of testicular fragments from N rats with a NO donor DETA-NOnoate (DETA-NO) induced germ cell apoptosis through external and internal apoptotic pathways, an effect prevented by N-acetyl-L-cysteine (NAC). DETA-NO inhibited testosterone released from Leydig cells, whereas NAC (from 2.5 to 15 mM) did not prevent this effect. Conclusions: We demonstrated that NO-NOS system is involved in the impairment of testicular function in orchitis. NO secreted mainly by testicular macrophages could promote oxidative stress inducing ST damage and interfering in Leydig cell function.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
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/11336/15190
Jarazo Dietrich, Sabrina Soledad; Fass, Mónica Irina; Jacobo, Patricia Verónica; Sobarzo, Cristian Marcelo Alejandro; Lustig, Livia; et al.; Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion; Public Library of Science; Plos One; 10; 6; 6-2015; e0128709
1932-6203
url http://hdl.handle.net/11336/15190
identifier_str_mv Jarazo Dietrich, Sabrina Soledad; Fass, Mónica Irina; Jacobo, Patricia Verónica; Sobarzo, Cristian Marcelo Alejandro; Lustig, Livia; et al.; Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion; Public Library of Science; Plos One; 10; 6; 6-2015; e0128709
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128709
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0128709
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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