Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Silva, Paula Letícia Braga
Orientador(a): Monteiro, Helena Serra Azul
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/34403
Resumo: The renal system through multiple actions exerts homeostasis of the body. Several complications cause damage and damage the structure and also decrease the functional activity of the kidneys, triggering a clinical condition called Acute Renal Injury (AKI). Compounds containing metal ions are used with great relevance in the treatment of different diseases. In the last years, the chemistry of nitrosyl metal complexes has become significant due to the important role involving transition metal in the biological processes of NO. This paper aims to study the renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular Ischemia / Reperfusion (I / R) models. The experiments to evaluate renal hemodynamic effects were performed with kidney isolated from Wistar rats and biochemical measurements of the collected samples were performed and quantification of cGMP by ELISA. I/R model in vitro were performed in LLC-MK2 renal tubule cells line and cell respiration assay by flow cytometry through the analysis of mitochondrial transmembrane potential with Rhodamine 123 dye. The project was approved by the Ethics Committee on Use of Animals (CEUA)/UFC under protocol number 102/2016. In compound kidney infusion compound FOR011B caused increased perfusion pressure and renal vascular resistance. The FOR011B and FOR811B increased urinary flow and decreased osmolar clearence and TFG. They also caused a decrease in the total and proximal transport of sodium, potassium and chloride. Only FOR011B increased levels of urinary GMPc of perfused kidneys. In LLC-MK2 cells line, only FOR 811 A demonstrated potential protective effect of respiratory dysfunction caused by I/R injury and, also caused increased nitrite / nitrate (NOx) concentration in renal tissue. In short, future experiments are needed to investigate the mechanism by which the FOR811B has the capacity of donate nitric oxide in a controlled manner and at subtoxic levels.
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spelling Silva, Paula Letícia BragaMonteiro, Helena Serra Azul2018-07-25T17:11:14Z2018-07-25T17:11:14Z2018-07-16SILVA, P. L. B. Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular. 2018. 97 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/34403The renal system through multiple actions exerts homeostasis of the body. Several complications cause damage and damage the structure and also decrease the functional activity of the kidneys, triggering a clinical condition called Acute Renal Injury (AKI). Compounds containing metal ions are used with great relevance in the treatment of different diseases. In the last years, the chemistry of nitrosyl metal complexes has become significant due to the important role involving transition metal in the biological processes of NO. This paper aims to study the renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular Ischemia / Reperfusion (I / R) models. The experiments to evaluate renal hemodynamic effects were performed with kidney isolated from Wistar rats and biochemical measurements of the collected samples were performed and quantification of cGMP by ELISA. I/R model in vitro were performed in LLC-MK2 renal tubule cells line and cell respiration assay by flow cytometry through the analysis of mitochondrial transmembrane potential with Rhodamine 123 dye. The project was approved by the Ethics Committee on Use of Animals (CEUA)/UFC under protocol number 102/2016. In compound kidney infusion compound FOR011B caused increased perfusion pressure and renal vascular resistance. The FOR011B and FOR811B increased urinary flow and decreased osmolar clearence and TFG. They also caused a decrease in the total and proximal transport of sodium, potassium and chloride. Only FOR011B increased levels of urinary GMPc of perfused kidneys. In LLC-MK2 cells line, only FOR 811 A demonstrated potential protective effect of respiratory dysfunction caused by I/R injury and, also caused increased nitrite / nitrate (NOx) concentration in renal tissue. In short, future experiments are needed to investigate the mechanism by which the FOR811B has the capacity of donate nitric oxide in a controlled manner and at subtoxic levels.O sistema renal através de múltiplas ações exerce homeostasia do corpo. Diversas complicações causam danos e danificam a estrutura e, também, diminuem a atividade funcional dos rins, desencadeando um estado clínico denominado Lesão Renal Aguda (LRA). Compostos contendo íons metálicos são utilizados com grande relevância no tratamentos de diferentes doenças. Nos últimos anos, a química dos complexos de metal nitrosilos, tornou-se significativo devido ao papel importante envolvendo metal de transição nos processos biológicos de NO. O presente trabalho tem como objetivo estudar os efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e Isquemia/Reperfusão (I/R) celular. Os experimentos para avaliação dos efeitos hemodinâmicos renais foram realizados com rim isolado de ratos Wistar e, realizou-se dosagens bioquímicas das amostras coletadas e quantificação de GMPc por ELISA. Realizou-se também modelo in vitro de I/R em linhagens de células tubulares renais LLC-MK2 e ensaio de respiração celular por citometria de fluxo através da análise do potencial transmembrânico mitocondrial com corante Rodamina 123. O projeto foi aprovado pelo Comitê de Ética no Uso de animais CEUA/UFC sob o número de protocolo 102/2016. Em perfusão de rim isolado o composto FOR011B causou aumento da pressão de perfusão e resistência vascular renal. O FOR011B e FOR811B aumentaram o fluxo urinário, clearence osmolar e reduziram TFG. Também ocasionaram diminuição dos transportes totais e proximais de sódio, potássio e cloreto. Somente o FOR011B aumentou os níveis de GMPc urinário dos rins perfundidos. Em linhagem de células LLC-MK2, apenas o FOR811B demonstrou potencial efeito protetor da disfunção respiratória causada pela lesão por I/R e, também, causou aumento da concentração nitrito/nitrato (NOx) em tecido renal. Em suma, faz-se necessário futuros experimentos para investigar o mecanismo pelo qual o FOR811B tem a capacidade de doar óxido nítrico de maneira controlada e em níveis subtóxicos.Óxido NítricoTraumatismo por ReperfusãoLesão Renal AgudaIsquemiaEfeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celularThe renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular ischemia / reperfusion (I/R) modelsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2018_dis_plbsilva.pdf2018_dis_plbsilva.pdfapplication/pdf1360416http://repositorio.ufc.br/bitstream/riufc/34403/1/2018_dis_plbsilva.pdf9dcf57462967ecb0b8ad203b2bfa6ddfMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81812http://repositorio.ufc.br/bitstream/riufc/34403/2/license.txt9351db63ea91b32e01910aaf21c0fd0aMD52riufc/344032019-10-16 09:51:16.768oai:repositorio.ufc.br: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ório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-16T12:51:16Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
dc.title.en.pt_BR.fl_str_mv The renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular ischemia / reperfusion (I/R) models
title Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
spellingShingle Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
Silva, Paula Letícia Braga
Óxido Nítrico
Traumatismo por Reperfusão
Lesão Renal Aguda
Isquemia
title_short Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
title_full Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
title_fullStr Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
title_full_unstemmed Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
title_sort Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular
author Silva, Paula Letícia Braga
author_facet Silva, Paula Letícia Braga
author_role author
dc.contributor.author.fl_str_mv Silva, Paula Letícia Braga
dc.contributor.advisor1.fl_str_mv Monteiro, Helena Serra Azul
contributor_str_mv Monteiro, Helena Serra Azul
dc.subject.por.fl_str_mv Óxido Nítrico
Traumatismo por Reperfusão
Lesão Renal Aguda
Isquemia
topic Óxido Nítrico
Traumatismo por Reperfusão
Lesão Renal Aguda
Isquemia
description The renal system through multiple actions exerts homeostasis of the body. Several complications cause damage and damage the structure and also decrease the functional activity of the kidneys, triggering a clinical condition called Acute Renal Injury (AKI). Compounds containing metal ions are used with great relevance in the treatment of different diseases. In the last years, the chemistry of nitrosyl metal complexes has become significant due to the important role involving transition metal in the biological processes of NO. This paper aims to study the renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular Ischemia / Reperfusion (I / R) models. The experiments to evaluate renal hemodynamic effects were performed with kidney isolated from Wistar rats and biochemical measurements of the collected samples were performed and quantification of cGMP by ELISA. I/R model in vitro were performed in LLC-MK2 renal tubule cells line and cell respiration assay by flow cytometry through the analysis of mitochondrial transmembrane potential with Rhodamine 123 dye. The project was approved by the Ethics Committee on Use of Animals (CEUA)/UFC under protocol number 102/2016. In compound kidney infusion compound FOR011B caused increased perfusion pressure and renal vascular resistance. The FOR011B and FOR811B increased urinary flow and decreased osmolar clearence and TFG. They also caused a decrease in the total and proximal transport of sodium, potassium and chloride. Only FOR011B increased levels of urinary GMPc of perfused kidneys. In LLC-MK2 cells line, only FOR 811 A demonstrated potential protective effect of respiratory dysfunction caused by I/R injury and, also caused increased nitrite / nitrate (NOx) concentration in renal tissue. In short, future experiments are needed to investigate the mechanism by which the FOR811B has the capacity of donate nitric oxide in a controlled manner and at subtoxic levels.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-07-25T17:11:14Z
dc.date.available.fl_str_mv 2018-07-25T17:11:14Z
dc.date.issued.fl_str_mv 2018-07-16
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dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv SILVA, P. L. B. Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular. 2018. 97 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/34403
identifier_str_mv SILVA, P. L. B. Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular. 2018. 97 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
url http://www.repositorio.ufc.br/handle/riufc/34403
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