Sildenafil previne a nefropatia induzida por contraste em ratos wistar
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/8011 |
Resumo: | Despite being one of the most common causes of acute renal failure in hospitalized patients, the contrast-induced nephropathy (CIN) is a common but poorly understood problem and does not have an appropriate treatment. Studies report on the antioxidant action of phosphodiesterase 5 inhibitors. Therefore, we investigated if sildenafil can prevent or ameliorate kidney dysfunction in an experimental model of CIN in rats. Male Wistar rats (290-390 g) were treated for 7 days by gavage with sildenafil (50 mg/kg/day) or vehicle (2ml/kg/day). The acute nephropathy was induced by water restriction (24 hr), L-NAME and indomethacin injection (10mg / kg i.p.) and contrast medium injection (iohexol 3mg/Kg i.v.) or saline, resulting in the following experimental groups: control, CIN, CIN + sildenafil. After, was made the analysis of renal function including assessment of the glomerular filtration rate (GFR), renal blood flow (RBF), renal plasma flow (RPF) and renal vascular resistance (RVR) by determining the clearance of inulin and para-aminohippurate, and investigation of oxidative stress at the molecular level (flow cytometry). Values are expressed as means ± S.E.M. one-way ANOVA followed by Tukey´s post hoc test. A value of p<0.05 was regarded as statistically significant. Contrast administration has resulted in decline in GFR (control: 8.53 ± 0.55; CIN: 3.77 ± 0.26*; CIN + S: 6.77 ± 0.39*# mL/min/Kg), RPF(control: 20.04 ± 0.9; CIN: 9.59 ± 0.38*; CIN + S:13.18 ± 0.26* # mL/min/Kg) and RBF(control: 35.01 ± 2.02, ± 0.67*; CIN: 20,36; NIC + S: 22.46 ± 0.8* # mL/min/Kg) and increased RVR (control: 3.59 ± 0.46; CIN: 7.72 ± 0.31 *; CIN + S: 4.86 ± 0.17# a.u), which was prevented by treatment with sildenafil. Therefore, sildenafil may be a promising therapeutic agent for the prevention and / or treatment of renal dysfunction induced by contrast. |
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Pereira, Thiago de Melo CostaGava, Ágata LagesPrates, Laís Salles de AlmeidaMeyrelles, Silvana dos SantosGraceli, Jones Bernardes2018-08-01T22:58:49Z2018-08-012018-08-01T22:58:49Z2015-08-31Despite being one of the most common causes of acute renal failure in hospitalized patients, the contrast-induced nephropathy (CIN) is a common but poorly understood problem and does not have an appropriate treatment. Studies report on the antioxidant action of phosphodiesterase 5 inhibitors. Therefore, we investigated if sildenafil can prevent or ameliorate kidney dysfunction in an experimental model of CIN in rats. Male Wistar rats (290-390 g) were treated for 7 days by gavage with sildenafil (50 mg/kg/day) or vehicle (2ml/kg/day). The acute nephropathy was induced by water restriction (24 hr), L-NAME and indomethacin injection (10mg / kg i.p.) and contrast medium injection (iohexol 3mg/Kg i.v.) or saline, resulting in the following experimental groups: control, CIN, CIN + sildenafil. After, was made the analysis of renal function including assessment of the glomerular filtration rate (GFR), renal blood flow (RBF), renal plasma flow (RPF) and renal vascular resistance (RVR) by determining the clearance of inulin and para-aminohippurate, and investigation of oxidative stress at the molecular level (flow cytometry). Values are expressed as means ± S.E.M. one-way ANOVA followed by Tukey´s post hoc test. A value of p<0.05 was regarded as statistically significant. Contrast administration has resulted in decline in GFR (control: 8.53 ± 0.55; CIN: 3.77 ± 0.26*; CIN + S: 6.77 ± 0.39*# mL/min/Kg), RPF(control: 20.04 ± 0.9; CIN: 9.59 ± 0.38*; CIN + S:13.18 ± 0.26* # mL/min/Kg) and RBF(control: 35.01 ± 2.02, ± 0.67*; CIN: 20,36; NIC + S: 22.46 ± 0.8* # mL/min/Kg) and increased RVR (control: 3.59 ± 0.46; CIN: 7.72 ± 0.31 *; CIN + S: 4.86 ± 0.17# a.u), which was prevented by treatment with sildenafil. Therefore, sildenafil may be a promising therapeutic agent for the prevention and / or treatment of renal dysfunction induced by contrast.Apesar de ser uma das causas mais comuns de insuficiência renal aguda em pacientes hospitalizados, a nefropatia induzida por contraste (NIC) é um problema comum mas mal compreendido e não possui um tratamento adequado. Estudos têm demonstrado a ação antioxidante dos inibidores da fosfodiesterase-5. Portanto, nós investigamos se o sildenafil pode prevenir a disfunção renal de ratos submetidos ao meio de contraste. Ratos Wistar machos (250-350g) foram tratados, durante 7 dias, por gavagem, com sildenafil (50 mg/Kg/dia) ou veículo (2mL/Kg/dia). A NIC foi induzida através da restrição hídrica (24h), injeção i.p. (10mg/Kg) de L-NAME e indometacina, além da injeção i.v. (3mg/Kg) de meio de contraste (Iohexol) ou salina, resultando nos seguintes grupos experimentais: Controle, NIC e NIC + Sildenafil. Em seguida foi feita a análise hemodinâmica renal por padrões-ouro (clerarance de inulina e paraaminohipurato) aliando alterações funcionais acrescidas de investigações a nível molecular (citometria de fluxo). Dados expressos como Média ± EPM; ANOVA 1 via; post-hoc de Tukey; *p<0,05 vs. controle e #p<0.05 vs. NIC. A administração do contraste resultou em queda da taxa de filtração glomerular (controle: 8,53 ± 0,55; NIC: 3,77 ± 0,26* ; NIC + S: 6,77 ± 0,39*# mL/min/Kg), do fluxo plasmático renal (controle: 20,04 ± 0,9; NIC: 9,59 ± 0,38*; NIC + S: 13,18 ± 0,26*# mL/min/Kg ) e do fluxo sanguíneo renal (controle: 35,01 ± 2,02; NIC20,36 ± 0,67*; NIC + S: 22,46 ± 0,8 *# mL/min/Kg ) e aumento da resistência vascular renal (controle: 3,59 ± 0,46; NIC: 7,72 ± 0,31*; NIC + S: 4,86 ± 0,17# u.a), os quais foram prevenidos pelo tratamento com sildenafil. Portanto, o sildenafil pode ser um promissor agente terapêutico para a prevenção e / ou tratamento de disfunção renal induzida por contraste.Texthttp://repositorio.ufes.br/handle/10/8011porUniversidade Federal do Espírito SantoMestrado em Ciências FisiológicasPrograma de Pós-Graduação em Ciências FisiológicasUFESBRCentro de Ciências da SaúdeContrast-induced nephropathy (CIN)Oxidative stressSildenafilNefropatia induzida por contraste (NIC)Estresse oxidativoFisiologia612Sildenafil previne a nefropatia induzida por contraste em ratos wistarinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALtese_9228_Dissertação Laís Salles de Almeida.pdfapplication/pdf2594681http://repositorio.ufes.br/bitstreams/eb6f7f2f-d699-423f-b090-55cf22d8c838/downloadc15623bf46832d3d0475e42e67efdd24MD5110/80112024-07-16 17:04:38.441oai:repositorio.ufes.br:10/8011http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-10-15T17:55:23.016287Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
title |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
spellingShingle |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar Prates, Laís Salles de Almeida Contrast-induced nephropathy (CIN) Oxidative stress Sildenafil Nefropatia induzida por contraste (NIC) Estresse oxidativo Fisiologia 612 |
title_short |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
title_full |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
title_fullStr |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
title_full_unstemmed |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
title_sort |
Sildenafil previne a nefropatia induzida por contraste em ratos wistar |
author |
Prates, Laís Salles de Almeida |
author_facet |
Prates, Laís Salles de Almeida |
author_role |
author |
dc.contributor.advisor-co1.fl_str_mv |
Pereira, Thiago de Melo Costa |
dc.contributor.advisor1.fl_str_mv |
Gava, Ágata Lages |
dc.contributor.author.fl_str_mv |
Prates, Laís Salles de Almeida |
dc.contributor.referee1.fl_str_mv |
Meyrelles, Silvana dos Santos |
dc.contributor.referee2.fl_str_mv |
Graceli, Jones Bernardes |
contributor_str_mv |
Pereira, Thiago de Melo Costa Gava, Ágata Lages Meyrelles, Silvana dos Santos Graceli, Jones Bernardes |
dc.subject.eng.fl_str_mv |
Contrast-induced nephropathy (CIN) Oxidative stress |
topic |
Contrast-induced nephropathy (CIN) Oxidative stress Sildenafil Nefropatia induzida por contraste (NIC) Estresse oxidativo Fisiologia 612 |
dc.subject.por.fl_str_mv |
Sildenafil Nefropatia induzida por contraste (NIC) Estresse oxidativo |
dc.subject.cnpq.fl_str_mv |
Fisiologia |
dc.subject.udc.none.fl_str_mv |
612 |
description |
Despite being one of the most common causes of acute renal failure in hospitalized patients, the contrast-induced nephropathy (CIN) is a common but poorly understood problem and does not have an appropriate treatment. Studies report on the antioxidant action of phosphodiesterase 5 inhibitors. Therefore, we investigated if sildenafil can prevent or ameliorate kidney dysfunction in an experimental model of CIN in rats. Male Wistar rats (290-390 g) were treated for 7 days by gavage with sildenafil (50 mg/kg/day) or vehicle (2ml/kg/day). The acute nephropathy was induced by water restriction (24 hr), L-NAME and indomethacin injection (10mg / kg i.p.) and contrast medium injection (iohexol 3mg/Kg i.v.) or saline, resulting in the following experimental groups: control, CIN, CIN + sildenafil. After, was made the analysis of renal function including assessment of the glomerular filtration rate (GFR), renal blood flow (RBF), renal plasma flow (RPF) and renal vascular resistance (RVR) by determining the clearance of inulin and para-aminohippurate, and investigation of oxidative stress at the molecular level (flow cytometry). Values are expressed as means ± S.E.M. one-way ANOVA followed by Tukey´s post hoc test. A value of p<0.05 was regarded as statistically significant. Contrast administration has resulted in decline in GFR (control: 8.53 ± 0.55; CIN: 3.77 ± 0.26*; CIN + S: 6.77 ± 0.39*# mL/min/Kg), RPF(control: 20.04 ± 0.9; CIN: 9.59 ± 0.38*; CIN + S:13.18 ± 0.26* # mL/min/Kg) and RBF(control: 35.01 ± 2.02, ± 0.67*; CIN: 20,36; NIC + S: 22.46 ± 0.8* # mL/min/Kg) and increased RVR (control: 3.59 ± 0.46; CIN: 7.72 ± 0.31 *; CIN + S: 4.86 ± 0.17# a.u), which was prevented by treatment with sildenafil. Therefore, sildenafil may be a promising therapeutic agent for the prevention and / or treatment of renal dysfunction induced by contrast. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-08-31 |
dc.date.accessioned.fl_str_mv |
2018-08-01T22:58:49Z |
dc.date.available.fl_str_mv |
2018-08-01 2018-08-01T22:58:49Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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http://repositorio.ufes.br/handle/10/8011 |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
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Programa de Pós-Graduação em Ciências Fisiológicas |
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UFES |
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BR |
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Centro de Ciências da Saúde |
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Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
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Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
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