Sildenafil previne a nefropatia induzida por contraste em ratos wistar

Detalhes bibliográficos
Autor(a) principal: Prates, Laís Salles de Almeida
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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spelling 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
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2018-08-01T22:58:49Z
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dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Mestrado em Ciências Fisiológicas
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dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Mestrado em Ciências Fisiológicas
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