Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: DOLFINI, Pedro Meira lattes
Orientador(a): Mendes, Leonardo de Oliveira lattes
Banca de defesa: Rossi, Renata Calciolari lattes, Silva, Débora Tavares de Resende e 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 Ciências da Saúde
Departamento: Mestrado em Ciências da Saúde
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/1657
Resumo: The kidneys are essential organs for several homeostatic functions, but they are vulnerable to damage caused by exposure to environmental chemicals, especially endocrine disruptors (ED). These compounds can interfere with the endocrine system and are associated with a number of adverse health effects, including kidney injury and nephrotoxicity. Exposure to ED during fetal development is of particular concern because it can lead to long-lasting structural and functional changes in the kidney, predisposing to kidney disease in adulthood. Therefore, the aim of this study was to characterize the effects of perinatal exposure to a mixture of ED on renal histoarchitecture. Pregnant Sprague-Dawley rats were randomly divided into 2 experimental groups: Control Group (vehicle: corn oil, by gavage) and ED Mix Group: received 32.11 mg/kg/day of the mixture consisting of twelve compounds (phthalates, pesticides, UV filters, bisphenol A, butylparaben) diluted in corn oil (2 ml/kg), by gavage. Pregnant or lactating rats received treatment from gestational day 7 (GD7) to postnatal day 21 (PND21). After weaning, on PND22, the pups were housed until 440 days of age receiving water and food ad libitum, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were subjected to fractal analysis, karyometric analysis, glomerular volume analysis, nuclear perimeter, elongation factor and quantification of collagen types. The DE mixture did not alter the organosomatic index and absolute weight of the kidney. In the animals exposed to the mixture, lesions such as necrosis and tubular fusion were observed, verifying a biological tendency (p = 0.068) for a greater number of histological alterations in the exposed group. An increase in the nuclear perimeter and the presence of larger nuclei were observed in the cortex (p < 0.5) and medulla (p = 0,003) of animals exposed to the mixture, in addition to changes in the pattern of cellular organization in the glomerular and medullary regions of these animals. Exposure to the DE mixture altered the pattern of renal collagen organization, increased fibrosis represented by the increase in collagen I and III in the cortical and medullary compartments (p < 0.0001) and reduced the amount in the glomerulus. These findings suggest that perinatal exposure to ED may significantly affect the histoarchitecture of the renal microenvironment during aging, indicating that the environment may impact renal function and health across the lifespan.
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spelling Mendes, Leonardo de Oliveirahttp://lattes.cnpq.br/3362264138327486Rossi, Renata Calciolarihttp://lattes.cnpq.br/9313445810035844Silva, Débora Tavares de Resende ehttp://lattes.cnpq.br/6093255618062496http://lattes.cnpq.br/7417823440048884DOLFINI, Pedro Meira2025-03-10T14:43:22Z2024-08-29DOLFINI, Pedro Meira. Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos. 2024. Dissertação (Mestrado em Ciências da Saúde) - Universidade do Oeste Paulista, Presidente Prudente, SP, 2024.http://bdtd.unoeste.br:8080/jspui/handle/jspui/1657The kidneys are essential organs for several homeostatic functions, but they are vulnerable to damage caused by exposure to environmental chemicals, especially endocrine disruptors (ED). These compounds can interfere with the endocrine system and are associated with a number of adverse health effects, including kidney injury and nephrotoxicity. Exposure to ED during fetal development is of particular concern because it can lead to long-lasting structural and functional changes in the kidney, predisposing to kidney disease in adulthood. Therefore, the aim of this study was to characterize the effects of perinatal exposure to a mixture of ED on renal histoarchitecture. Pregnant Sprague-Dawley rats were randomly divided into 2 experimental groups: Control Group (vehicle: corn oil, by gavage) and ED Mix Group: received 32.11 mg/kg/day of the mixture consisting of twelve compounds (phthalates, pesticides, UV filters, bisphenol A, butylparaben) diluted in corn oil (2 ml/kg), by gavage. Pregnant or lactating rats received treatment from gestational day 7 (GD7) to postnatal day 21 (PND21). After weaning, on PND22, the pups were housed until 440 days of age receiving water and food ad libitum, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were subjected to fractal analysis, karyometric analysis, glomerular volume analysis, nuclear perimeter, elongation factor and quantification of collagen types. The DE mixture did not alter the organosomatic index and absolute weight of the kidney. In the animals exposed to the mixture, lesions such as necrosis and tubular fusion were observed, verifying a biological tendency (p = 0.068) for a greater number of histological alterations in the exposed group. An increase in the nuclear perimeter and the presence of larger nuclei were observed in the cortex (p < 0.5) and medulla (p = 0,003) of animals exposed to the mixture, in addition to changes in the pattern of cellular organization in the glomerular and medullary regions of these animals. Exposure to the DE mixture altered the pattern of renal collagen organization, increased fibrosis represented by the increase in collagen I and III in the cortical and medullary compartments (p < 0.0001) and reduced the amount in the glomerulus. These findings suggest that perinatal exposure to ED may significantly affect the histoarchitecture of the renal microenvironment during aging, indicating that the environment may impact renal function and health across the lifespan.Os rins são órgãos essenciais para diversas funções homeostáticas, porém são vulneráveis a danos causados por exposição a produtos químicos ambientais, especialmente desreguladores endócrinos (DE). Esses compostos podem interferir no sistema endócrino e estão associados a uma série de efeitos adversos à saúde, incluindo lesões renais e nefrotoxicidade. A exposição a DE durante o desenvolvimento fetal é particularmente preocupante, pois pode levar a modificações estruturais e funcionais duradouras nos rins, predispondo a doenças renais na vida adulta. Assim, o objetivo do estudo foi caracterizar os efeitos da exposição perinatal a uma mistura de DE sobre a histoarquitetura renal. Fêmeas prenhas da linhagem Sprague-Dawley foram divididas aleatoriamente em 2 grupos experimentais: Grupo Controle: receberam veículo (óleo de milho, 2 ml/kg, por gavagem) e Grupo ED Mix: receberam 32,11 mg/kg/dia da mistura constituída de doze compostos (ftalatos, pesticidas, filtros u.v., bisfenol A, butilparabeno) diluídos em óleo de milho (2 ml/kg), por gavagem. As ratas prenhas ou lactentes recebem o tratamento do dia gestacional 7 (DG7) até o dia pós-natal 21 (DPN21). Após o desmame, no DPN22, os filhotes ficaram alojados até os 440 dias de idade recebendo água e ração ad libitum, 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. A mistura de DE não alterou o índice organo-somático e peso absoluto do rim. Nos animais expostos à mistura foram observadas lesões como necrose e fusão tubular verificando uma tendência biológica (p = 0,068) para um maior número de alterações patológicas no grupo exposto. Verificou-se aumento do perímetro nuclear e a presença de núcleos maiores no córtex (p < 0,0001) e na medula (p = 0,003) de animais expostos à mistura, além de alteração no padrão de organização celular nas regiões glomerulares (p < 0,0001) e medular (p = 0,0018) destes animais. A exposição à mistura de DE alterou o padrão de organização do colágeno renal, aumentou a fibrose representada pelo aumento do colágeno I e III nos compartimentos cortical e medular (p < 0,0001) e reduziu a quantidade no glomérulo (p < 0,0001). Esses achados sugerem que a exposição perinatal a DE pode alterar a histoarquitetura do microambiente renal durante o envelhecimento, indicando que o ambiente pode impactar na função renal e a saúde ao longo da vida.Submitted by Jakeline Ortega (jakortega@unoeste.br) on 2025-03-10T14:43:22Z No. of bitstreams: 1 Defesa - Pedro Meira Dolfini (1).pdf: 1946070 bytes, checksum: ff9b5440c413ff8571b473ec659d1830 (MD5)Made available in DSpace on 2025-03-10T14:43:22Z (GMT). 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dc.title.por.fl_str_mv Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
dc.title.alternative.eng.fl_str_mv Influence of perinatal exposure to an endocrine disruptor mixture on the renal microenvironment in aged rats: histopathological aspects
title Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
spellingShingle Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
DOLFINI, Pedro Meira
Nefropatia
Desreguladores endócrinos
Efeitos retardados da exposição pré-natal
Nephropathy
Endocrine disruptors
Prenatal exposure delayed effects.
CIENCIAS DA SAUDE::MEDICINA
title_short Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
title_full Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
title_fullStr Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
title_full_unstemmed Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
title_sort Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos
author DOLFINI, Pedro Meira
author_facet DOLFINI, Pedro Meira
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 Rossi, Renata Calciolari
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9313445810035844
dc.contributor.referee2.fl_str_mv Silva, Débora Tavares de Resende e
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/6093255618062496
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7417823440048884
dc.contributor.author.fl_str_mv DOLFINI, Pedro Meira
contributor_str_mv Mendes, Leonardo de Oliveira
Rossi, Renata Calciolari
Silva, Débora Tavares de Resende e
dc.subject.por.fl_str_mv Nefropatia
Desreguladores endócrinos
Efeitos retardados da exposição pré-natal
topic Nefropatia
Desreguladores endócrinos
Efeitos retardados da exposição pré-natal
Nephropathy
Endocrine disruptors
Prenatal exposure delayed effects.
CIENCIAS DA SAUDE::MEDICINA
dc.subject.eng.fl_str_mv Nephropathy
Endocrine disruptors
Prenatal exposure delayed effects.
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::MEDICINA
description The kidneys are essential organs for several homeostatic functions, but they are vulnerable to damage caused by exposure to environmental chemicals, especially endocrine disruptors (ED). These compounds can interfere with the endocrine system and are associated with a number of adverse health effects, including kidney injury and nephrotoxicity. Exposure to ED during fetal development is of particular concern because it can lead to long-lasting structural and functional changes in the kidney, predisposing to kidney disease in adulthood. Therefore, the aim of this study was to characterize the effects of perinatal exposure to a mixture of ED on renal histoarchitecture. Pregnant Sprague-Dawley rats were randomly divided into 2 experimental groups: Control Group (vehicle: corn oil, by gavage) and ED Mix Group: received 32.11 mg/kg/day of the mixture consisting of twelve compounds (phthalates, pesticides, UV filters, bisphenol A, butylparaben) diluted in corn oil (2 ml/kg), by gavage. Pregnant or lactating rats received treatment from gestational day 7 (GD7) to postnatal day 21 (PND21). After weaning, on PND22, the pups were housed until 440 days of age receiving water and food ad libitum, when they were euthanized. The kidney was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin and picrosirius were subjected to fractal analysis, karyometric analysis, glomerular volume analysis, nuclear perimeter, elongation factor and quantification of collagen types. The DE mixture did not alter the organosomatic index and absolute weight of the kidney. In the animals exposed to the mixture, lesions such as necrosis and tubular fusion were observed, verifying a biological tendency (p = 0.068) for a greater number of histological alterations in the exposed group. An increase in the nuclear perimeter and the presence of larger nuclei were observed in the cortex (p < 0.5) and medulla (p = 0,003) of animals exposed to the mixture, in addition to changes in the pattern of cellular organization in the glomerular and medullary regions of these animals. Exposure to the DE mixture altered the pattern of renal collagen organization, increased fibrosis represented by the increase in collagen I and III in the cortical and medullary compartments (p < 0.0001) and reduced the amount in the glomerulus. These findings suggest that perinatal exposure to ED may significantly affect the histoarchitecture of the renal microenvironment during aging, indicating that the environment may impact renal function and health across the lifespan.
publishDate 2024
dc.date.issued.fl_str_mv 2024-08-29
dc.date.accessioned.fl_str_mv 2025-03-10T14:43:22Z
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dc.identifier.citation.fl_str_mv DOLFINI, Pedro Meira. Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos. 2024. Dissertação (Mestrado em Ciências da Saúde) - Universidade do Oeste Paulista, Presidente Prudente, SP, 2024.
dc.identifier.uri.fl_str_mv http://bdtd.unoeste.br:8080/jspui/handle/jspui/1657
identifier_str_mv DOLFINI, Pedro Meira. Influência de desreguladores endócrinos no microambiente renal de ratos durante o envelhecimento: aspectos histopatológicos. 2024. Dissertação (Mestrado em Ciências da Saúde) - Universidade do Oeste Paulista, Presidente Prudente, SP, 2024.
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