Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Sousa, José Kleybson de
Orientador(a): Lima, Aldo Ângelo Moreira
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/76940
Resumo: Child malnutrition is considered a serious public health problem as it is associated with high mortality rates, cognitive and growth deficits. The use of translational preclinical models is essential for the search for more appropriate treatments and is important to reduce the morbidity associated with malnutrition. Therefore, the objective of this work was to evaluate the intestinal epithelial barrier function of mice subject to an animal model of acute malnutrition based on the complementary diet of children with malnutrition described in the MAL-ED multicenter COHORT study and to investigate whether treatment with glutamine reverses the changes caused. For the induction of experimental malnutrition, male C57BL/6 mice (21 days old) were fed the MAL-ED diet for 12 days. As a treatment, glutamine was used continuously (final concentration of 31.4 mM in drinking water) for five days, starting on the eighth day after starting the diet. Another group of animals received the same concentration of isonitrogenic glycine, to investigate the results found in glutamine treatment were caused by increased nitrogen levels. On days 0, 7 and 12 of the experimental protocol, body composition and body development were measured. The intestinal barrier function was measured using electrophysiological parameters of Potential Difference - DP, Short Circuit Current - Isc and Transepithelial Resistance - Basal Rt and absorption of glucose, glutamine, and alanyl-glutamine. Mice subjected to the MAL-ED diet showed a reduction in fat mass, weight gain, and body growth. The analyzes in automatized Ussing Chamber System (UCS) showed an increase in Rt in relation to the cumulative concentrations of glutamine and alanyl-glutamine, reducing the low absorption of substrates in animals that consumed the MAL-ED diet. Treatment with glutamine reversed weight loss and promoted improvement in body growth, an increase in basal Rt and an improvement in the intestinal epithelial barrier function in animals that consumed the MAL-ED diet. According to the findings of the present study, the MAL-ED diet causes changes in the gastrointestinal barrier. Furthermore, it demonstrated the use of glutamine as a new mechanism for effectiveness in improving weight gain and growth in malnourished animals by restoring the function of the intestinal epithelial barrier.
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spelling Sousa, José Kleybson deMoore, Sean R.Lima, Aldo Ângelo Moreira2024-05-23T13:15:19Z2024-05-23T13:15:19Z2023SOUSA, José Kleybson de. Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino. 2023. 334 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/76940. Acesso em:23 maio 2024.http://repositorio.ufc.br/handle/riufc/76940Child malnutrition is considered a serious public health problem as it is associated with high mortality rates, cognitive and growth deficits. The use of translational preclinical models is essential for the search for more appropriate treatments and is important to reduce the morbidity associated with malnutrition. Therefore, the objective of this work was to evaluate the intestinal epithelial barrier function of mice subject to an animal model of acute malnutrition based on the complementary diet of children with malnutrition described in the MAL-ED multicenter COHORT study and to investigate whether treatment with glutamine reverses the changes caused. For the induction of experimental malnutrition, male C57BL/6 mice (21 days old) were fed the MAL-ED diet for 12 days. As a treatment, glutamine was used continuously (final concentration of 31.4 mM in drinking water) for five days, starting on the eighth day after starting the diet. Another group of animals received the same concentration of isonitrogenic glycine, to investigate the results found in glutamine treatment were caused by increased nitrogen levels. On days 0, 7 and 12 of the experimental protocol, body composition and body development were measured. The intestinal barrier function was measured using electrophysiological parameters of Potential Difference - DP, Short Circuit Current - Isc and Transepithelial Resistance - Basal Rt and absorption of glucose, glutamine, and alanyl-glutamine. Mice subjected to the MAL-ED diet showed a reduction in fat mass, weight gain, and body growth. The analyzes in automatized Ussing Chamber System (UCS) showed an increase in Rt in relation to the cumulative concentrations of glutamine and alanyl-glutamine, reducing the low absorption of substrates in animals that consumed the MAL-ED diet. Treatment with glutamine reversed weight loss and promoted improvement in body growth, an increase in basal Rt and an improvement in the intestinal epithelial barrier function in animals that consumed the MAL-ED diet. According to the findings of the present study, the MAL-ED diet causes changes in the gastrointestinal barrier. Furthermore, it demonstrated the use of glutamine as a new mechanism for effectiveness in improving weight gain and growth in malnourished animals by restoring the function of the intestinal epithelial barrier.A desnutrição infantil é considerada um grave problema de saúde pública, pois está associada a altas taxas de mortalidade, déficits cognitivos e de crescimento. O uso de modelos pré-clínicos translacionais é essencial para buscar tratamentos mais adequados e importante para reduzir a morbidade associada à desnutrição. Desta forma, o objetivo deste trabalho foi avaliar a função da barreira epitelial intestinal de camundongos sujeitos a um modelo animal de desnutrição aguda baseado na dieta complementar de crianças com desnutrição, conforme descrito no estudo COORTE multicêntrico MAL-ED, e investigar se o tratamento com glutamina reverte as alterações causadas. Para induzir a desnutrição experimental, camundongos C57BL/6 machos (21 dias de idade) foram alimentados com a dieta MAL-ED por 12 dias. Como tratamento, a glutamina foi usada continuamente (com uma concentração final de 31,4 mM na água de beber) por cinco dias, iniciando no oitavo dia após o início da dieta. Outro grupo de animais recebeu a mesma concentração de glicina isonitrogênica, para investigar se os resultados encontrados no tratamento com glutamina foram causados pelo aumento dos níveis de nitrogênio. Nos dias 0, 7 e 12 do protocolo experimental, a composição corporal e o desenvolvimento corporal foram mensurados. A função de barreira intestinal foi mensurada utilizando parâmetros eletrofisiológicos de Diferença de Potencial (DP), Corrente de Curto-Circuito (CCC) e Resistência Transepitelial (Rt) basais, bem como na absorção de glicose, glutamina e alanil-glutamina. Camundongos submetidos à dieta MAL-ED apresentaram redução da massa gorda, ganho de peso e crescimento corporal. As análises realizadas no sistema automatizado de Câmaras de Ussing (SCU) indicaram aumento da Rt frente a concentrações cumulativas de glutamina e alanil-glutamina, o que sugere baixa absorção desses substratos nos animais que consumiram a dieta MAL-ED. Por outro lado, o tratamento com glutamina reverteu a perda de peso, promoveu melhora no crescimento corporal e aumentou a Rt basal, além de melhorar a função da barreira epitelial intestinal nos animais que consumiram a dieta MAL-ED. De acordo com os achados do presente estudo, a dieta MAL-ED causa alterações na barreira gastrointestinal e evidenciou-se o uso da glutamina como um novo mecanismo para melhorar o ganho de peso e o crescimento de animais desnutridos, por meio da restauração da função da barreira epitelial intestinal.Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murinoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSaúde PúblicaDesnutriçãoFunção da Barreira IntestinalPublic HealthIntestinal Barrier FunctionMalnutritionCNPQ::CIENCIAS DA SAUDE::MEDICINAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0003-3512-484Xhttp://lattes.cnpq.br/2288008491790035https://orcid.org/0000-0002-0299-1747http://lattes.cnpq.br/2153321168945169http://lattes.cnpq.br/1695331316300249ORIGINAL2023_tese_jkdsousa.pdf.pdf2023_tese_jkdsousa.pdf.pdfapplication/pdf22990891http://repositorio.ufc.br/bitstream/riufc/76940/1/2023_tese_jkdsousa.pdf.pdf05f24b0b83dfd65780a4d186910a4bc7MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/76940/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/769402024-05-23 10:18:35.115oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-05-23T13:18:35Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
title Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
spellingShingle Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
Sousa, José Kleybson de
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Saúde Pública
Desnutrição
Função da Barreira Intestinal
Public Health
Intestinal Barrier Function
Malnutrition
title_short Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
title_full Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
title_fullStr Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
title_full_unstemmed Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
title_sort Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino
author Sousa, José Kleybson de
author_facet Sousa, José Kleybson de
author_role author
dc.contributor.co-advisor.none.fl_str_mv Moore, Sean R.
dc.contributor.author.fl_str_mv Sousa, José Kleybson de
dc.contributor.advisor1.fl_str_mv Lima, Aldo Ângelo Moreira
contributor_str_mv Lima, Aldo Ângelo Moreira
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA
Saúde Pública
Desnutrição
Função da Barreira Intestinal
Public Health
Intestinal Barrier Function
Malnutrition
dc.subject.ptbr.pt_BR.fl_str_mv Saúde Pública
Desnutrição
Função da Barreira Intestinal
dc.subject.en.pt_BR.fl_str_mv Public Health
Intestinal Barrier Function
Malnutrition
description Child malnutrition is considered a serious public health problem as it is associated with high mortality rates, cognitive and growth deficits. The use of translational preclinical models is essential for the search for more appropriate treatments and is important to reduce the morbidity associated with malnutrition. Therefore, the objective of this work was to evaluate the intestinal epithelial barrier function of mice subject to an animal model of acute malnutrition based on the complementary diet of children with malnutrition described in the MAL-ED multicenter COHORT study and to investigate whether treatment with glutamine reverses the changes caused. For the induction of experimental malnutrition, male C57BL/6 mice (21 days old) were fed the MAL-ED diet for 12 days. As a treatment, glutamine was used continuously (final concentration of 31.4 mM in drinking water) for five days, starting on the eighth day after starting the diet. Another group of animals received the same concentration of isonitrogenic glycine, to investigate the results found in glutamine treatment were caused by increased nitrogen levels. On days 0, 7 and 12 of the experimental protocol, body composition and body development were measured. The intestinal barrier function was measured using electrophysiological parameters of Potential Difference - DP, Short Circuit Current - Isc and Transepithelial Resistance - Basal Rt and absorption of glucose, glutamine, and alanyl-glutamine. Mice subjected to the MAL-ED diet showed a reduction in fat mass, weight gain, and body growth. The analyzes in automatized Ussing Chamber System (UCS) showed an increase in Rt in relation to the cumulative concentrations of glutamine and alanyl-glutamine, reducing the low absorption of substrates in animals that consumed the MAL-ED diet. Treatment with glutamine reversed weight loss and promoted improvement in body growth, an increase in basal Rt and an improvement in the intestinal epithelial barrier function in animals that consumed the MAL-ED diet. According to the findings of the present study, the MAL-ED diet causes changes in the gastrointestinal barrier. Furthermore, it demonstrated the use of glutamine as a new mechanism for effectiveness in improving weight gain and growth in malnourished animals by restoring the function of the intestinal epithelial barrier.
publishDate 2023
dc.date.issued.fl_str_mv 2023
dc.date.accessioned.fl_str_mv 2024-05-23T13:15:19Z
dc.date.available.fl_str_mv 2024-05-23T13:15:19Z
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dc.identifier.citation.fl_str_mv SOUSA, José Kleybson de. Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino. 2023. 334 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/76940. Acesso em:23 maio 2024.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/76940
identifier_str_mv SOUSA, José Kleybson de. Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino. 2023. 334 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/76940. Acesso em:23 maio 2024.
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