Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi

Detalhes bibliográficos
Ano de defesa: 2010
Autor(a) principal: Sousa, Daniel Freire de
Orientador(a): Monteiro, Helena Serra Azul
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
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
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/77803
Resumo: Toxinology is a science dedicated to the study of toxins derived from microorganisms, plants and animals; as it is closely related to health biotechnology, it allows to reveal the mechanisms of action of toxins, to develop pharmacological tools, new treatment protocols and to improve better prognoses. The study of toxins of new species of snakes such as Bothrops lutzi is Included in this context. The aim of this study was to evaluate the renal and vascular changes promoted by the snake B. lutzi venom. Studies with isolated rat kidneys were performed in a perfusion system that allows to evaluate possible changes in renal parameters; further studies with renal tubular epithelial cells of dog (MDCK), permitted to observe the possible expression of pro-apoptotic genes. We studied also the possible vascular changes induced by this venom in aortic rings and mesenteric vascular beds. The results showed that the B. lutzi venom of (BLV) induced significant changes in all renal parameters studied, mainly the reduction of perfusion pressure (PPcontrol somin = 108.69±5.08mmHg vs. PPBLV 1.0pg/mL somin = 73.55±2.79mmHg) and renal vascular resistance (RVRcontrol somin = 5.32±0.57mmHg. mL-1. g-1. min-1 vs. RVRBLv 1.0pg/mL somin = 3.39±0.30mmHg. mL 1. g-1. min-1), while increasing urinary flow (UFcontroi 120min = 0.160±0.020 mL.g-1. min-1VS. UFBLV 10.0pg/mL 120min = 0.981±0.103mL.g-1. min-1) and glomerular filtration rate (GFR conntrol 120min = 0.697±0.084 mL.g-1. min-1 vs. GFRBLv 10.0Ng/mL 12omin = 3.152±0.342mL.g-1. min-1) in at least one of the concentrations studied. The most relevant fact is that this poison is highly toxic to the renal tubules, and this fact was demonstrated by the decrease of the percentage of transport of sodium (Na +), potassium (K +) and chloride (Cl-) in all concentrations, regardless of PP reduction. These parameters were reduced by at least 10.0% when compared to controls. Tubular damages were also observed by histological analysis (evidence of apoptosis/direct cellular damage); reduction of MDCK cell viability was noticed up to 92.34% (BLV 100.0pg/mL); the expression of pro-apoptotic genes CASP- 3 and CASP-8 was not observed in this protocol (CASP-3control =1.09±0.08 vs. CASP-3BLV=1.01±0.08; CASP-8control= 1.04±0.05 vs. CASP-8BLv=0.93±0.06). PP reduction seems to be related to the relaxation of renal vessels of which vasodilatory effects were observed in aortic rings, with relaxation of 23.89% (BLV 20.0pg/mL), though we have not observed such effects in the mesenteric vascular bed. Thus, B. lutzi venom seems to affect mainly renal tubules, independently from the vascular actions; in addition, cellular death has occurred regardless of nonexpression of pro-apoptotic genes.
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spelling Sousa, Daniel Freire deMonteiro, Helena Serra Azul2024-08-21T18:40:32Z2024-08-21T18:40:32Z2010SOUSA, Daniel Freire de. Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi. 2010. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2010.http://repositorio.ufc.br/handle/riufc/77803Toxinology is a science dedicated to the study of toxins derived from microorganisms, plants and animals; as it is closely related to health biotechnology, it allows to reveal the mechanisms of action of toxins, to develop pharmacological tools, new treatment protocols and to improve better prognoses. The study of toxins of new species of snakes such as Bothrops lutzi is Included in this context. The aim of this study was to evaluate the renal and vascular changes promoted by the snake B. lutzi venom. Studies with isolated rat kidneys were performed in a perfusion system that allows to evaluate possible changes in renal parameters; further studies with renal tubular epithelial cells of dog (MDCK), permitted to observe the possible expression of pro-apoptotic genes. We studied also the possible vascular changes induced by this venom in aortic rings and mesenteric vascular beds. The results showed that the B. lutzi venom of (BLV) induced significant changes in all renal parameters studied, mainly the reduction of perfusion pressure (PPcontrol somin = 108.69±5.08mmHg vs. PPBLV 1.0pg/mL somin = 73.55±2.79mmHg) and renal vascular resistance (RVRcontrol somin = 5.32±0.57mmHg. mL-1. g-1. min-1 vs. RVRBLv 1.0pg/mL somin = 3.39±0.30mmHg. mL 1. g-1. min-1), while increasing urinary flow (UFcontroi 120min = 0.160±0.020 mL.g-1. min-1VS. UFBLV 10.0pg/mL 120min = 0.981±0.103mL.g-1. min-1) and glomerular filtration rate (GFR conntrol 120min = 0.697±0.084 mL.g-1. min-1 vs. GFRBLv 10.0Ng/mL 12omin = 3.152±0.342mL.g-1. min-1) in at least one of the concentrations studied. The most relevant fact is that this poison is highly toxic to the renal tubules, and this fact was demonstrated by the decrease of the percentage of transport of sodium (Na +), potassium (K +) and chloride (Cl-) in all concentrations, regardless of PP reduction. These parameters were reduced by at least 10.0% when compared to controls. Tubular damages were also observed by histological analysis (evidence of apoptosis/direct cellular damage); reduction of MDCK cell viability was noticed up to 92.34% (BLV 100.0pg/mL); the expression of pro-apoptotic genes CASP- 3 and CASP-8 was not observed in this protocol (CASP-3control =1.09±0.08 vs. CASP-3BLV=1.01±0.08; CASP-8control= 1.04±0.05 vs. CASP-8BLv=0.93±0.06). PP reduction seems to be related to the relaxation of renal vessels of which vasodilatory effects were observed in aortic rings, with relaxation of 23.89% (BLV 20.0pg/mL), though we have not observed such effects in the mesenteric vascular bed. Thus, B. lutzi venom seems to affect mainly renal tubules, independently from the vascular actions; in addition, cellular death has occurred regardless of nonexpression of pro-apoptotic genes.A toxinologia é a ciência que se dedica ao estudo de toxinas derivadas de microrganismos, plantas e animais, estando intimamente relacionada com a Biotecnologia em Saúde, uma vez que possibilita desvendar os mecanismos de ação das toxinas, desenvolvendo ferramentas farmacológicas, novos protocolos de tratamentos e favorecendo a melhores prognóstico. Inclui-se nesse contexto o estudo de toxinas de novas espécies de serpentes, como a Bothrops lutzi. O objetivo do presente trabalho foi avaliar as alterações renais e vasculares promovidas pelo veneno total da serpente B. lutzi. Os estudos em rim isolado de rato foram realizados em um sistema de perfusão que permite avaliar as possíveis alterações dos parâmetros renais, além de estudos com células epiteliais de túbulos renais de cachorro (MDCK), observando-se a possível expressão de genes pró-apoptóticos. Estudaram-se, ainda, as possíveis alterações vasculares induzidas por esse veneno em anéis de aorta e leitos vasculares mesentéricos. Os resultados encontrados demonstraram que a peçonha de B. lutzi (VBL) promoveu alterações significativas em todos os parâmetros renais estudados, principalmente na diminuição da pressão de perfusão (PPcontroie 90min = 108,69±5,08mmHg vs. PPVBL 1,0pg/mL 90min = 73,55±2,79mmHg) e da resistência vascular renal (RVRcontroie 90min = 5,32±0,57mmHg. mL"1. g-1. min-1 vs. RVRvBL 1,0pg/mL 90min = 3,39±0,30mmHg. mL-1. g-1. min-1), além do aumento do fluxo urinário (FUcontroie 120min = 0,160±0,020 mL.g-1. min-1 vs. FUvBL 10,0Ng/mL 120min = 0,981±0,103mL.g-1. min-1) e do ritmo de filtração glomerular (RFGcontroie 120min = 0,697±0,084 mL.g"1. min-1 vs. RFGvBL 10,opg/mL 12omin = 3,152±0,342mL.g"1. min-1) em pelo menos uma das concentrações estudadas. O dado mais relevante é que essa peçonha é altamente lesiva aos túbulos renais, sendo tal fato demonstrado com a redução do percentual de transporte dos eletrólitos sódio (Na+), potássio (K+) e cloreto (Cl) " em todas as concentrações estudadas, independentemente da redução da PP, onde esses parâmetros foram reduzidos em pelo menos 10,0% quando comparado aos controles. Também foram observadas lesões tubulares nas análises histológicas (indícios de apoptose/dano celular direto), bem como foi constatada redução da viabilidade das células MDCK em até 92,34%(VBL 100pg/mL); não se verificou a expressão de genes pró-apoptóticos CASP-3 e CASP-8 nesse protocolo (CASP-3controie=1,09±0,08 vs. CASP-3VBL=1,01±0,08; CASP-8controie= 1,04±0,05 vs. CASP-8vBL=0,93±0,06). A redução da PP parece estar relacionada ao relaxamento de vasos renais, cujos efeitos vasodilatadores foram observados nos anéis de aorta, com relaxamento de 23,89% (VBL 20,0pg/mL) embora não se tenha observado tais efeitos em leito vascular mesentérico. Assim, o veneno de B. lutzi parece comprometer principalmente os túbulos renais, independentemente das ações vasculares, além da morte celular ter ocorrido independentemente da expressão de genes pró-aoptóticos.Este documento está disponível online com base na Portaria nº 348, de 08 de dezembro de 2022, disponível em: https://biblioteca.ufc.br/wp-content/uploads/2022/12/portaria348-2022.pdf, que autoriza a digitalização e a disponibilização no Repositório Institucional (RI) da coleção retrospectiva de TCC, dissertações e teses da UFC, sem o termo de anuência prévia dos autores. Em caso de trabalhos com pedidos de patente e/ou de embargo, cabe, exclusivamente, ao autor(a) solicitar a restrição de acesso ou retirada de seu trabalho do RI, mediante apresentação de documento comprobatório à Direção do Sistema de Bibliotecas.Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisToxicologiaRinsVasos sanguíneosCNPQ::CIENCIAS BIOLOGICASinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/4573933755133756http://lattes.cnpq.br/38301557076595192024-08-12ORIGINAL2010_tese_dfsousa.pdf2010_tese_dfsousa.pdfapplication/pdf22396123http://repositorio.ufc.br/bitstream/riufc/77803/1/2010_tese_dfsousa.pdf5b0e833bc55feb73241a527d7f9aa7e7MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/77803/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/778032024-08-21 15:40:33.372oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-08-21T18:40:33Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
title Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
spellingShingle Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
Sousa, Daniel Freire de
CNPQ::CIENCIAS BIOLOGICAS
Toxicologia
Rins
Vasos sanguíneos
title_short Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
title_full Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
title_fullStr Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
title_full_unstemmed Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
title_sort Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi
author Sousa, Daniel Freire de
author_facet Sousa, Daniel Freire de
author_role author
dc.contributor.author.fl_str_mv Sousa, Daniel Freire de
dc.contributor.advisor1.fl_str_mv Monteiro, Helena Serra Azul
contributor_str_mv Monteiro, Helena Serra Azul
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS
topic CNPQ::CIENCIAS BIOLOGICAS
Toxicologia
Rins
Vasos sanguíneos
dc.subject.ptbr.pt_BR.fl_str_mv Toxicologia
Rins
Vasos sanguíneos
description Toxinology is a science dedicated to the study of toxins derived from microorganisms, plants and animals; as it is closely related to health biotechnology, it allows to reveal the mechanisms of action of toxins, to develop pharmacological tools, new treatment protocols and to improve better prognoses. The study of toxins of new species of snakes such as Bothrops lutzi is Included in this context. The aim of this study was to evaluate the renal and vascular changes promoted by the snake B. lutzi venom. Studies with isolated rat kidneys were performed in a perfusion system that allows to evaluate possible changes in renal parameters; further studies with renal tubular epithelial cells of dog (MDCK), permitted to observe the possible expression of pro-apoptotic genes. We studied also the possible vascular changes induced by this venom in aortic rings and mesenteric vascular beds. The results showed that the B. lutzi venom of (BLV) induced significant changes in all renal parameters studied, mainly the reduction of perfusion pressure (PPcontrol somin = 108.69±5.08mmHg vs. PPBLV 1.0pg/mL somin = 73.55±2.79mmHg) and renal vascular resistance (RVRcontrol somin = 5.32±0.57mmHg. mL-1. g-1. min-1 vs. RVRBLv 1.0pg/mL somin = 3.39±0.30mmHg. mL 1. g-1. min-1), while increasing urinary flow (UFcontroi 120min = 0.160±0.020 mL.g-1. min-1VS. UFBLV 10.0pg/mL 120min = 0.981±0.103mL.g-1. min-1) and glomerular filtration rate (GFR conntrol 120min = 0.697±0.084 mL.g-1. min-1 vs. GFRBLv 10.0Ng/mL 12omin = 3.152±0.342mL.g-1. min-1) in at least one of the concentrations studied. The most relevant fact is that this poison is highly toxic to the renal tubules, and this fact was demonstrated by the decrease of the percentage of transport of sodium (Na +), potassium (K +) and chloride (Cl-) in all concentrations, regardless of PP reduction. These parameters were reduced by at least 10.0% when compared to controls. Tubular damages were also observed by histological analysis (evidence of apoptosis/direct cellular damage); reduction of MDCK cell viability was noticed up to 92.34% (BLV 100.0pg/mL); the expression of pro-apoptotic genes CASP- 3 and CASP-8 was not observed in this protocol (CASP-3control =1.09±0.08 vs. CASP-3BLV=1.01±0.08; CASP-8control= 1.04±0.05 vs. CASP-8BLv=0.93±0.06). PP reduction seems to be related to the relaxation of renal vessels of which vasodilatory effects were observed in aortic rings, with relaxation of 23.89% (BLV 20.0pg/mL), though we have not observed such effects in the mesenteric vascular bed. Thus, B. lutzi venom seems to affect mainly renal tubules, independently from the vascular actions; in addition, cellular death has occurred regardless of nonexpression of pro-apoptotic genes.
publishDate 2010
dc.date.issued.fl_str_mv 2010
dc.date.accessioned.fl_str_mv 2024-08-21T18:40:32Z
dc.date.available.fl_str_mv 2024-08-21T18:40:32Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv SOUSA, Daniel Freire de. Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi. 2010. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2010.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/77803
identifier_str_mv SOUSA, Daniel Freire de. Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi. 2010. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2010.
url http://repositorio.ufc.br/handle/riufc/77803
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