Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Hinokuma, Karianne Delalibera lattes
Orientador(a): Mendes, Leonardo de Oliveira lattes
Banca de defesa: Castilho, Anthony César de Souza lattes, Santos, Cristiane dos lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade do Oeste Paulista
Programa de Pós-Graduação: Mestrado em Ciência Animal
Departamento: Mestrado em Ciência Animal
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://bdtd.unoeste.br:8080/jspui/handle/jspui/1495
Resumo: Synthetic compounds have long been introduced into human everyday life. The exposome concept has been proposed as the assessment of environmental exposures and associated biological responses over a lifetime. Disseminated in the environment, endocrine disruptors (ED) are capable of modifying hormone biosynthesis, which may cause instabilities in human health. Because they have bioaccumulation as their main characteristic, the kidney becomes a potential target of ED. Thus, researches using experimental protocols that mimic human exposure throughout life are important to characterize the effects of ED on health/homeostasis, especially in the kidney, an important organ within this internal balance system. Thus, the aim of the present study was to evaluate cellular and tissue changes, in addition to oxidative stress, in the kidney of rats exposed during pregnancy, lactation and even adulthood to an ED mixture based on human exposure. Pregnant females of the Sprague-Dawley strain were randomly divided into 2 experimental groups: Ctrl Group (vehicle: corn oil, by gavage) and ED Mix group: they received 32.11mg/kg/day of a mixture consisting of twelve compounds (phthalates, pesticides , u.v. filters, bisphenol A, butylparaben) diluted in corn oil (2ml/kg), by gavage. Pregnant or lactating rats received the treatment from gestational day 7 (DG7) until postnatal day 21 (DPN21). After weaning, at DPN22, the male offspring of the F1 generation continued to receive the complete EDmixture until they were 220 days old, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were submitted to fractal and kariometric analysis, analysis of glomerular volume, nuclear perimeter, elongation factor and quantification of collagen types. In addition, oxidative stress was performed. No changes were observed in the biometric data. Nuclear alterations were dependent on the evaluated compartment, with the ED mixture favoring the presence of elliptical nuclei in the cortical and glomerular region and more rounded nuclei in the medullary region. ED mixture caused an increase in renal fibrosis in all compartments, without altering antioxidant enzymes. In view of this, we conclude that environmentally relevant exposure to a ED mixture causes nuclear changes and induces renal fibrosis.
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spelling Mendes, Leonardo de Oliveirahttp://lattes.cnpq.br/3362264138327486Castilho, Anthony César de Souzahttp://lattes.cnpq.br/0480944334194184Santos, Cristiane doshttp://lattes.cnpq.br/2900820531617905http://lattes.cnpq.br/0158812012021227Hinokuma, Karianne Delalibera2023-05-26T11:58:29Z2023-02-24Hinokuma, Karianne Delalibera. Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos. 2023. 69F. Dissertação (Mestrado em Ciência Animal) - Universidade do Oeste Paulista, Presidente Prudente, 2023.http://bdtd.unoeste.br:8080/jspui/handle/jspui/1495Synthetic compounds have long been introduced into human everyday life. The exposome concept has been proposed as the assessment of environmental exposures and associated biological responses over a lifetime. Disseminated in the environment, endocrine disruptors (ED) are capable of modifying hormone biosynthesis, which may cause instabilities in human health. Because they have bioaccumulation as their main characteristic, the kidney becomes a potential target of ED. Thus, researches using experimental protocols that mimic human exposure throughout life are important to characterize the effects of ED on health/homeostasis, especially in the kidney, an important organ within this internal balance system. Thus, the aim of the present study was to evaluate cellular and tissue changes, in addition to oxidative stress, in the kidney of rats exposed during pregnancy, lactation and even adulthood to an ED mixture based on human exposure. Pregnant females of the Sprague-Dawley strain were randomly divided into 2 experimental groups: Ctrl Group (vehicle: corn oil, by gavage) and ED Mix group: they received 32.11mg/kg/day of a mixture consisting of twelve compounds (phthalates, pesticides , u.v. filters, bisphenol A, butylparaben) diluted in corn oil (2ml/kg), by gavage. Pregnant or lactating rats received the treatment from gestational day 7 (DG7) until postnatal day 21 (DPN21). After weaning, at DPN22, the male offspring of the F1 generation continued to receive the complete EDmixture until they were 220 days old, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were submitted to fractal and kariometric analysis, analysis of glomerular volume, nuclear perimeter, elongation factor and quantification of collagen types. In addition, oxidative stress was performed. No changes were observed in the biometric data. Nuclear alterations were dependent on the evaluated compartment, with the ED mixture favoring the presence of elliptical nuclei in the cortical and glomerular region and more rounded nuclei in the medullary region. ED mixture caused an increase in renal fibrosis in all compartments, without altering antioxidant enzymes. In view of this, we conclude that environmentally relevant exposure to a ED mixture causes nuclear changes and induces renal fibrosis.Há tempos compostos sintéticos foram introduzidos no cotidiano dos humanos. O conceito do expossoma foi proposto como a avaliação das exposições ambientais e das respostas biológicas associadas ao longo da vida. Disseminados no ambiente, os desreguladores endócrinos (DE) são capazes de modificar a biossíntese hormonal, podendo provocar instabilidades na saúde humana. Por possuírem como característica principal a bioacumulação, o rim torna-se um alvo em potencial dos DE. Desta forma, pesquisas que utilizem protocolos experimentais que mimetizam a exposição humana ao longo da vida são importantes para caracterizar os efeitos dos DE na saúde/homeostase, principalmente no rim, um órgão importante dentro deste sistema de equilíbrio interno. Assim, o objetivo do presente estudo foi avaliar as alterações celulares e teciduais, além do estresse oxidativo, no rim de ratos expostos durante gestação, lactação e até a vida adulta a uma mistura de DE baseada na exposição humana. Fêmeas prenhes da linhagem Sprague-Dawley foram divididas aleatoriamente em 2 grupos experimentais: Grupo Ctrl (veículo: óleo de milho, por gavagem) e Grupo ED Mix: receberam 32,11mg/kg/dia da mistura constituída de doze compostos (ftalatos, pesticidas, filtros u.v., bisfenol A, butilparabeno) diluídos em óleo de milho (2ml/kg), por gavagem. As ratas prenhes ou lactentes receberam o tratamento do dia gestacional 7 (DG7) até o dia pós-natal 21 (DPN21). Após o desmame, no DPN22, os filhotes machos da geração F1 continuaram a receber a mistura completa de DE até os 220 dias de idade, quando foram eutanasiados. O rim foi coletado, dissecado e processado para análise histológica. Secções coradas com hematoxilina-eosina e picrossírius foram submetidas à análise fractal, kariométrica, análise de volume glomerular, perímetro nuclear, fator de alongamento e quantificação dos tipos de colágeno. Além disso, foi realizado estresse oxidativo. Não foi observado alterações nos dados biométricos. As alterações nucleares foram dependentes do compartimento avaliado, com a mistura de DE favorecendo a presença de núcleos elípticos na região cortical e glomerular e núcleos mais arredondados na região medular. Mistura de DE provocou aumento de fibrose renal em todos os compartimentos, sem alteração das enzimas antioxidantes. Em vista disso, concluímos que a exposição ambientalmente relevante à uma mistura de DE provoca alterações nucleares e induz fibrose renal.Submitted by Michele Mologni (mologni@unoeste.br) on 2023-05-26T11:58:29Z No. of bitstreams: 1 Karianne Delalibera Hinokuma.pdf: 3277538 bytes, checksum: 66e7065cbffd75a795bfe2a713fd2971 (MD5)Made available in DSpace on 2023-05-26T11:58:29Z (GMT). No. of bitstreams: 1 Karianne Delalibera Hinokuma.pdf: 3277538 bytes, checksum: 66e7065cbffd75a795bfe2a713fd2971 (MD5) Previous issue date: 2023-02-24application/pdfhttp://bdtd.unoeste.br:8080/jspui/retrieve/5140/Karianne%20Delalibera%20Hinokuma.pdf.jpgporUniversidade do Oeste PaulistaMestrado em Ciência AnimalUNOESTEBrasilMestrado em Ciência Animaldisruptores endócrinos; rim; exposição ambiental; nefrotoxicidade.endocrine disruptors; kidney; enviromental exposure; nefrotoxicity.CIENCIAS AGRARIAS::MEDICINA VETERINARIAExposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratosChronic exposure to a mixture of endocrine disruptors alters the nuclear phenotype and induces renal fibrosis in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis18867256397436141355005006001886725639743614135453670264235017319info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UNOESTEinstname:Universidade do Oeste Paulista (UNOESTE)instacron:UNOESTETHUMBNAILKarianne Delalibera Hinokuma.pdf.jpgKarianne Delalibera Hinokuma.pdf.jpgimage/jpeg3558http://bdtd.unoeste.br:8080/tede/bitstream/jspui/1495/3/Karianne+Delalibera+Hinokuma.pdf.jpgfef7c1c0f4190b0cab60bd348653245fMD53ORIGINALKarianne Delalibera Hinokuma.pdfKarianne Delalibera Hinokuma.pdfapplication/pdf3277538http://bdtd.unoeste.br:8080/tede/bitstream/jspui/1495/2/Karianne+Delalibera+Hinokuma.pdf66e7065cbffd75a795bfe2a713fd2971MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82067http://bdtd.unoeste.br:8080/tede/bitstream/jspui/1495/1/license.txt47745281809acb27fb322a97f2d9cb88MD51jspui/14952023-05-27 01:00:35.01oai:bdtd.unoeste.br: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 Digital de Teses e Dissertaçõeshttp://bdtd.unoeste.br:8080/jspui/PUBhttp://bdtd.unoeste.br:8080/oai/requestbdtd@unoeste.bropendoar:2023-05-27T04:00:35Biblioteca Digital de Teses e Dissertações da UNOESTE - Universidade do Oeste Paulista (UNOESTE)false
dc.title.por.fl_str_mv Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
dc.title.alternative.eng.fl_str_mv Chronic exposure to a mixture of endocrine disruptors alters the nuclear phenotype and induces renal fibrosis in rats
title Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
spellingShingle Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
Hinokuma, Karianne Delalibera
disruptores endócrinos; rim; exposição ambiental; nefrotoxicidade.
endocrine disruptors; kidney; enviromental exposure; nefrotoxicity.
CIENCIAS AGRARIAS::MEDICINA VETERINARIA
title_short Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
title_full Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
title_fullStr Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
title_full_unstemmed Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
title_sort Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos
author Hinokuma, Karianne Delalibera
author_facet Hinokuma, Karianne Delalibera
author_role author
dc.contributor.advisor1.fl_str_mv Mendes, Leonardo de Oliveira
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3362264138327486
dc.contributor.referee1.fl_str_mv Castilho, Anthony César de Souza
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0480944334194184
dc.contributor.referee2.fl_str_mv Santos, Cristiane dos
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/2900820531617905
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0158812012021227
dc.contributor.author.fl_str_mv Hinokuma, Karianne Delalibera
contributor_str_mv Mendes, Leonardo de Oliveira
Castilho, Anthony César de Souza
Santos, Cristiane dos
dc.subject.por.fl_str_mv disruptores endócrinos; rim; exposição ambiental; nefrotoxicidade.
topic disruptores endócrinos; rim; exposição ambiental; nefrotoxicidade.
endocrine disruptors; kidney; enviromental exposure; nefrotoxicity.
CIENCIAS AGRARIAS::MEDICINA VETERINARIA
dc.subject.eng.fl_str_mv endocrine disruptors; kidney; enviromental exposure; nefrotoxicity.
dc.subject.cnpq.fl_str_mv CIENCIAS AGRARIAS::MEDICINA VETERINARIA
description Synthetic compounds have long been introduced into human everyday life. The exposome concept has been proposed as the assessment of environmental exposures and associated biological responses over a lifetime. Disseminated in the environment, endocrine disruptors (ED) are capable of modifying hormone biosynthesis, which may cause instabilities in human health. Because they have bioaccumulation as their main characteristic, the kidney becomes a potential target of ED. Thus, researches using experimental protocols that mimic human exposure throughout life are important to characterize the effects of ED on health/homeostasis, especially in the kidney, an important organ within this internal balance system. Thus, the aim of the present study was to evaluate cellular and tissue changes, in addition to oxidative stress, in the kidney of rats exposed during pregnancy, lactation and even adulthood to an ED mixture based on human exposure. Pregnant females of the Sprague-Dawley strain were randomly divided into 2 experimental groups: Ctrl Group (vehicle: corn oil, by gavage) and ED Mix group: they received 32.11mg/kg/day of a mixture consisting of twelve compounds (phthalates, pesticides , u.v. filters, bisphenol A, butylparaben) diluted in corn oil (2ml/kg), by gavage. Pregnant or lactating rats received the treatment from gestational day 7 (DG7) until postnatal day 21 (DPN21). After weaning, at DPN22, the male offspring of the F1 generation continued to receive the complete EDmixture until they were 220 days old, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were submitted to fractal and kariometric analysis, analysis of glomerular volume, nuclear perimeter, elongation factor and quantification of collagen types. In addition, oxidative stress was performed. No changes were observed in the biometric data. Nuclear alterations were dependent on the evaluated compartment, with the ED mixture favoring the presence of elliptical nuclei in the cortical and glomerular region and more rounded nuclei in the medullary region. ED mixture caused an increase in renal fibrosis in all compartments, without altering antioxidant enzymes. In view of this, we conclude that environmentally relevant exposure to a ED mixture causes nuclear changes and induces renal fibrosis.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-05-26T11:58:29Z
dc.date.issued.fl_str_mv 2023-02-24
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dc.identifier.citation.fl_str_mv Hinokuma, Karianne Delalibera. Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos. 2023. 69F. Dissertação (Mestrado em Ciência Animal) - Universidade do Oeste Paulista, Presidente Prudente, 2023.
dc.identifier.uri.fl_str_mv http://bdtd.unoeste.br:8080/jspui/handle/jspui/1495
identifier_str_mv Hinokuma, Karianne Delalibera. Exposição crônica a uma mistura de desreguladores endócrinos altera o fenótipo nuclear e induz fibrose renal em ratos. 2023. 69F. Dissertação (Mestrado em Ciência Animal) - Universidade do Oeste Paulista, Presidente Prudente, 2023.
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dc.publisher.department.fl_str_mv Mestrado em Ciência Animal
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