Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis

Detalhes bibliográficos
Autor(a) principal: Achar, Eduardo [UNIFESP]
Data de Publicação: 2009
Outros Autores: Maciel, Thiago T. [UNIFESP], Collares, Carlos F., Teixeira, Vicente de Paulo Castro [UNIFESP], Schor, Nestor [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1038/ki.2008.578
http://repositorio.unifesp.br/handle/11600/31335
Resumo: Amitriptyline is a pleiotropic tricyclic antidepressant, which has anti-oxidant and anti-inflammatory properties. We tested whether amitriptyline might be useful in the treatment of chronic renal disease using the mouse model of unilateral ureteral obstruction. Amitriptyline caused a significant reduction of interstitial fibrosis, determined by Masson's staining, with minimal myofibroblast formation and macrophage infiltration following ureteral obstruction. Using quantitative PCR we found that this treatment significantly reduced the expression of key molecular markers of progressive tubulointerstitial injury such as osteopontin, MCP-1, ICAM-1, and TGF-beta 1 compared to their level in a saline-treated control group. Sublethal X-irradiation or mycophenolate mofetil, treatments that reduce inflammation, were comparable to amitriptyline in the reduction of interstitial fibrosis and macrophage infiltration. These studies in animals suggest that amitriptyline is worth testing as a therapeutic agent that might preserve renal function by blocking inflammation and renal fibrosis.
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spelling Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosisamitriptylineinflammationtubulointerstitial fibrosisunilateral ureteral obstructionAmitriptyline is a pleiotropic tricyclic antidepressant, which has anti-oxidant and anti-inflammatory properties. We tested whether amitriptyline might be useful in the treatment of chronic renal disease using the mouse model of unilateral ureteral obstruction. Amitriptyline caused a significant reduction of interstitial fibrosis, determined by Masson's staining, with minimal myofibroblast formation and macrophage infiltration following ureteral obstruction. Using quantitative PCR we found that this treatment significantly reduced the expression of key molecular markers of progressive tubulointerstitial injury such as osteopontin, MCP-1, ICAM-1, and TGF-beta 1 compared to their level in a saline-treated control group. Sublethal X-irradiation or mycophenolate mofetil, treatments that reduce inflammation, were comparable to amitriptyline in the reduction of interstitial fibrosis and macrophage infiltration. These studies in animals suggest that amitriptyline is worth testing as a therapeutic agent that might preserve renal function by blocking inflammation and renal fibrosis.Universidade Federal de São Paulo, Div Nephrol, Dept Med, BR-04023900 São Paulo, BrazilSão Paulo City Univ UNICID, Dept Med, BR-04023900 São Paulo, BrazilSão Paulo Poison Control Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, BR-04023900 São Paulo, BrazilWeb of ScienceNature Publishing GroupUniversidade Federal de São Paulo (UNIFESP)São Paulo City Univ UNICIDSão Paulo Poison Control CtrAchar, Eduardo [UNIFESP]Maciel, Thiago T. [UNIFESP]Collares, Carlos F.Teixeira, Vicente de Paulo Castro [UNIFESP]Schor, Nestor [UNIFESP]2016-01-24T13:52:17Z2016-01-24T13:52:17Z2009-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion596-604http://dx.doi.org/10.1038/ki.2008.578Kidney International. New York: Nature Publishing Group, v. 75, n. 6, p. 596-604, 2009.10.1038/ki.2008.5780085-2538http://repositorio.unifesp.br/handle/11600/31335WOS:000263723200007engKidney Internationalinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2016-01-24T11:52:17Zoai:repositorio.unifesp.br/:11600/31335Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652016-01-24T11:52:17Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
title Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
spellingShingle Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
Achar, Eduardo [UNIFESP]
amitriptyline
inflammation
tubulointerstitial fibrosis
unilateral ureteral obstruction
title_short Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
title_full Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
title_fullStr Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
title_full_unstemmed Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
title_sort Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis
author Achar, Eduardo [UNIFESP]
author_facet Achar, Eduardo [UNIFESP]
Maciel, Thiago T. [UNIFESP]
Collares, Carlos F.
Teixeira, Vicente de Paulo Castro [UNIFESP]
Schor, Nestor [UNIFESP]
author_role author
author2 Maciel, Thiago T. [UNIFESP]
Collares, Carlos F.
Teixeira, Vicente de Paulo Castro [UNIFESP]
Schor, Nestor [UNIFESP]
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
São Paulo City Univ UNICID
São Paulo Poison Control Ctr
dc.contributor.author.fl_str_mv Achar, Eduardo [UNIFESP]
Maciel, Thiago T. [UNIFESP]
Collares, Carlos F.
Teixeira, Vicente de Paulo Castro [UNIFESP]
Schor, Nestor [UNIFESP]
dc.subject.por.fl_str_mv amitriptyline
inflammation
tubulointerstitial fibrosis
unilateral ureteral obstruction
topic amitriptyline
inflammation
tubulointerstitial fibrosis
unilateral ureteral obstruction
description Amitriptyline is a pleiotropic tricyclic antidepressant, which has anti-oxidant and anti-inflammatory properties. We tested whether amitriptyline might be useful in the treatment of chronic renal disease using the mouse model of unilateral ureteral obstruction. Amitriptyline caused a significant reduction of interstitial fibrosis, determined by Masson's staining, with minimal myofibroblast formation and macrophage infiltration following ureteral obstruction. Using quantitative PCR we found that this treatment significantly reduced the expression of key molecular markers of progressive tubulointerstitial injury such as osteopontin, MCP-1, ICAM-1, and TGF-beta 1 compared to their level in a saline-treated control group. Sublethal X-irradiation or mycophenolate mofetil, treatments that reduce inflammation, were comparable to amitriptyline in the reduction of interstitial fibrosis and macrophage infiltration. These studies in animals suggest that amitriptyline is worth testing as a therapeutic agent that might preserve renal function by blocking inflammation and renal fibrosis.
publishDate 2009
dc.date.none.fl_str_mv 2009-03-01
2016-01-24T13:52:17Z
2016-01-24T13:52:17Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1038/ki.2008.578
Kidney International. New York: Nature Publishing Group, v. 75, n. 6, p. 596-604, 2009.
10.1038/ki.2008.578
0085-2538
http://repositorio.unifesp.br/handle/11600/31335
WOS:000263723200007
url http://dx.doi.org/10.1038/ki.2008.578
http://repositorio.unifesp.br/handle/11600/31335
identifier_str_mv Kidney International. New York: Nature Publishing Group, v. 75, n. 6, p. 596-604, 2009.
10.1038/ki.2008.578
0085-2538
WOS:000263723200007
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Kidney International
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 596-604
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1814268383424675840

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