Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil

Detalhes bibliográficos
Autor(a) principal: Viviane Lima Batista
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/35844
Resumo: The 5 fluourouracil (5FU) is a chemotherapeutic agent used for the treatment of several types of cancer, the nonspecific mechanism of action of the drug leads to the development of side 5 effects, with intestinal mucositis being the most prevalent. Modulation of the microbiota may contribute to the protection of the epithelial barrier and intestinal homeostasis, and the use of probiotics has been studied due to its therapeutic potential in mucositis. Lactobacillus delbrueckii subsp. lactis CIDCA 133 has demonstrated probiotic potential both in vivo and in vitro. The present study evaluated the probiotic potential of the L. delbrueckii CIDCA 133 strain, 10 in its viable form, inactivated by heat (paraprobiotic) and its secreted products (postbiotics) in an experimental model of 5-FU-induced intestinal mucositis. For this, BALB/c mice (n=6/group) were divided, as follows: I-CTL (negative control), II-MUC (positive control), III MUC+MRS (culture medium control), IV-MUC+CIDCA 133 viable (probiotics), V- MUC+CIDCA 133 heat-inactivated (paraprobiotics), and VI- MUC+ SN CIDCA 133 viable (postbiotics). The 15 animals were treated by gavage with saline solution (group I and II), MRS (group III), CIDCA 133 viable 109 UFC/mL (group IV), CIDCA 133 heat-inactivated 109 CFU/mL (group V), and SN of CIDCA 133 viable (group VI) for 13 days. Intestinal mucositis was induced in groups II to VI with a single intraperitoneal injection of 5-FU (300 mg/kg) at 10° day of experimentation and was euthanized 72 hours later. The results demonstrate that probiotic, paraprobotic and 20 posbiotic were able to decrease the neutrophil inflammatory infiltrate and gene expression of the pro-inflammatory cytokine Il12p40, in addition to increasing the relative gene expression of Claudine (Cldn2). Supplementation with probiotics and paraprobotics were also able to negatively regulate the relative gene expression of Tnf and positively that of ll10. However, only the administration of probiotics was able to decrease the recruitment of eosinophils. 25 Similarly, only administration of probiotics was able to prevent increased inflammatory infiltrate of eosinophils, and only paraprobiotics prevents the increase of Il1b and the shortening of villus. Based on these results, the present study demonstrated that CIDCA 133 probiotic, paraprobiotic and postbiotic were able to partially attenuate the inflammatory and histopathological parameters of the intestinal mucositis induces by antineoplastic 5-FU, 30 however, new studies should be conducted to elucidate the mechanisms related to the beneficial effects found in the present study.
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spelling Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracilEffect of Lactobacillus delbrueckii CIDCA 133 and its products secreted on intestinal mucositis induced by 5-fluorouracilMucosite5-FUProbióticoParaprobióticoPosbióticoLactobacillus delbrueckii subsp. lactis CIDCA 133ImunomodulaçãoAtividade anti-inflamatóriaGenéticaMucositeFluoruracilaProbióticosLactobacillus delbrueckiiImunomodulaçãoAnti-inflamatóriosThe 5 fluourouracil (5FU) is a chemotherapeutic agent used for the treatment of several types of cancer, the nonspecific mechanism of action of the drug leads to the development of side 5 effects, with intestinal mucositis being the most prevalent. Modulation of the microbiota may contribute to the protection of the epithelial barrier and intestinal homeostasis, and the use of probiotics has been studied due to its therapeutic potential in mucositis. Lactobacillus delbrueckii subsp. lactis CIDCA 133 has demonstrated probiotic potential both in vivo and in vitro. The present study evaluated the probiotic potential of the L. delbrueckii CIDCA 133 strain, 10 in its viable form, inactivated by heat (paraprobiotic) and its secreted products (postbiotics) in an experimental model of 5-FU-induced intestinal mucositis. For this, BALB/c mice (n=6/group) were divided, as follows: I-CTL (negative control), II-MUC (positive control), III MUC+MRS (culture medium control), IV-MUC+CIDCA 133 viable (probiotics), V- MUC+CIDCA 133 heat-inactivated (paraprobiotics), and VI- MUC+ SN CIDCA 133 viable (postbiotics). The 15 animals were treated by gavage with saline solution (group I and II), MRS (group III), CIDCA 133 viable 109 UFC/mL (group IV), CIDCA 133 heat-inactivated 109 CFU/mL (group V), and SN of CIDCA 133 viable (group VI) for 13 days. Intestinal mucositis was induced in groups II to VI with a single intraperitoneal injection of 5-FU (300 mg/kg) at 10° day of experimentation and was euthanized 72 hours later. The results demonstrate that probiotic, paraprobotic and 20 posbiotic were able to decrease the neutrophil inflammatory infiltrate and gene expression of the pro-inflammatory cytokine Il12p40, in addition to increasing the relative gene expression of Claudine (Cldn2). Supplementation with probiotics and paraprobotics were also able to negatively regulate the relative gene expression of Tnf and positively that of ll10. However, only the administration of probiotics was able to decrease the recruitment of eosinophils. 25 Similarly, only administration of probiotics was able to prevent increased inflammatory infiltrate of eosinophils, and only paraprobiotics prevents the increase of Il1b and the shortening of villus. Based on these results, the present study demonstrated that CIDCA 133 probiotic, paraprobiotic and postbiotic were able to partially attenuate the inflammatory and histopathological parameters of the intestinal mucositis induces by antineoplastic 5-FU, 30 however, new studies should be conducted to elucidate the mechanisms related to the beneficial effects found in the present study.O 5 fluourouracil (5FU) é um agente quimioterápico usado para o tratamento de diversos tipos de câncer, o mecanismo de ação inespecífico deste fármaco leva o desenvolvimento de 5 efeitos colaterais, sendo a mucosite intestinal o mais prevalente. A modulação da microbiota pode contribuir com a proteção da barreira epitelial e homeostase intestinal, e o uso de probióticos tem sido estudado devido ao seu potencial terapêutico na mucosite. Lactobacillus delbrueckii subsp. lactis CIDCA 133 demonstrou potencial probiótico tanto in vivo como in vitro. O presente trabalho avaliou o potencial probiótico da linhagem L. delbrueckii CIDCA 133, 10 na sua forma viável, inativada por calor (paraprobiotico) e de seus produtos secretados (posbióticos) em um modelo experimental de mucosite intestinal induzida por 5-FU. Camundongos BALB/c foram divididos em 6 grupos (n=6), sendo eles: I-CLT (controle negativo), II- MUC (mucosite), III- MUC+MRS (mucosite tratado com caldo MRS), IV MUC+CIDCA 133 VIÁVEL (mucosite+probiótico), V- MUC+CIDCA 133 INATIVADA POR 15 CALOR (mucosite+paraprobiótico), VI- MUC+SOBRENADANTE (mucosite+posbiótico). Os animais receberam, intragastricamente, 300 μL de: solução salina (grupos I e II); meio MRS (grupo III); 109 UFC do probiótico (grupo IV); 109 UFC do paraprobiótico (grupo V) e; 300 μL do sobrenadante (posbiótico) (grupo VI), durante 13 dias. Os grupos II ao VI no 10° dia de experimentação receberam injeção intraperitoneal (ip) de 5-FU (300 mg/kg). Os animais foram 20 eutanasiados, 72 horas após a indução da inflamação. Os resultados demonstram que o probiótico, paraprobiótico e posbiótico foram capazes de diminuir o infiltrado inflamatório de neutrófilos e expressão gênica da citocina pro-inflamatória IL12p40, além de, aumentar a expressão gênica relativa de Claudina (Cldn2). A suplementação com o probiótico e paraprobiótico também foram capazes de regular negativamente a expressão gênica relativa 25 de Tnf e positivamente a de ll10. No entanto, apenas a administração do probiótico foi capaz de diminuir o recrutamento de eosinófilos. Bem como, o paraprobiótico foi capaz diminuir a expressão gênica de ll1b e prevenir o encurtamento das vilosidades. Com base nesses resultados, o presente trabalho demonstrou que CIDCA 133 probiótico, paraprobiótico e posbiótico foram capazes de atenuar parcialmente os parâmetros inflamatórios e 30 histopatológicos da mucosite intestinal induzida pelo antineoplásico 5-FU, no entanto, novos estudos devem ser conduzidos, visando elucidar os mecanismos relacionados aos efeitos benéficos encontrados no presente trabalho.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorUniversidade Federal de Minas GeraisBrasilICB - INSTITUTO DE CIÊNCIAS BIOLOGICASPrograma de Pós-Graduação em GenéticaUFMGVasco Ariston de Carvalho Azevedohttp://lattes.cnpq.br/1020477751003832Pamela Del Carmen Mancha AgrestiMariana Martins DrumondFlaviano dos Santos MartinsAngelica Thomaz VieiraAna Paula Trovatti UetanabaroViviane Lima Batista2021-04-27T20:42:54Z2021-04-27T20:42:54Z2021-03-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/35844porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2021-04-27T20:42:54Zoai:repositorio.ufmg.br:1843/35844Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2021-04-27T20:42:54Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
Effect of Lactobacillus delbrueckii CIDCA 133 and its products secreted on intestinal mucositis induced by 5-fluorouracil
title Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
spellingShingle Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
Viviane Lima Batista
Mucosite
5-FU
Probiótico
Paraprobiótico
Posbiótico
Lactobacillus delbrueckii subsp. lactis CIDCA 133
Imunomodulação
Atividade anti-inflamatória
Genética
Mucosite
Fluoruracila
Probióticos
Lactobacillus delbrueckii
Imunomodulação
Anti-inflamatórios
title_short Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
title_full Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
title_fullStr Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
title_full_unstemmed Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
title_sort Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil
author Viviane Lima Batista
author_facet Viviane Lima Batista
author_role author
dc.contributor.none.fl_str_mv Vasco Ariston de Carvalho Azevedo
http://lattes.cnpq.br/1020477751003832
Pamela Del Carmen Mancha Agresti
Mariana Martins Drumond
Flaviano dos Santos Martins
Angelica Thomaz Vieira
Ana Paula Trovatti Uetanabaro
dc.contributor.author.fl_str_mv Viviane Lima Batista
dc.subject.por.fl_str_mv Mucosite
5-FU
Probiótico
Paraprobiótico
Posbiótico
Lactobacillus delbrueckii subsp. lactis CIDCA 133
Imunomodulação
Atividade anti-inflamatória
Genética
Mucosite
Fluoruracila
Probióticos
Lactobacillus delbrueckii
Imunomodulação
Anti-inflamatórios
topic Mucosite
5-FU
Probiótico
Paraprobiótico
Posbiótico
Lactobacillus delbrueckii subsp. lactis CIDCA 133
Imunomodulação
Atividade anti-inflamatória
Genética
Mucosite
Fluoruracila
Probióticos
Lactobacillus delbrueckii
Imunomodulação
Anti-inflamatórios
description The 5 fluourouracil (5FU) is a chemotherapeutic agent used for the treatment of several types of cancer, the nonspecific mechanism of action of the drug leads to the development of side 5 effects, with intestinal mucositis being the most prevalent. Modulation of the microbiota may contribute to the protection of the epithelial barrier and intestinal homeostasis, and the use of probiotics has been studied due to its therapeutic potential in mucositis. Lactobacillus delbrueckii subsp. lactis CIDCA 133 has demonstrated probiotic potential both in vivo and in vitro. The present study evaluated the probiotic potential of the L. delbrueckii CIDCA 133 strain, 10 in its viable form, inactivated by heat (paraprobiotic) and its secreted products (postbiotics) in an experimental model of 5-FU-induced intestinal mucositis. For this, BALB/c mice (n=6/group) were divided, as follows: I-CTL (negative control), II-MUC (positive control), III MUC+MRS (culture medium control), IV-MUC+CIDCA 133 viable (probiotics), V- MUC+CIDCA 133 heat-inactivated (paraprobiotics), and VI- MUC+ SN CIDCA 133 viable (postbiotics). The 15 animals were treated by gavage with saline solution (group I and II), MRS (group III), CIDCA 133 viable 109 UFC/mL (group IV), CIDCA 133 heat-inactivated 109 CFU/mL (group V), and SN of CIDCA 133 viable (group VI) for 13 days. Intestinal mucositis was induced in groups II to VI with a single intraperitoneal injection of 5-FU (300 mg/kg) at 10° day of experimentation and was euthanized 72 hours later. The results demonstrate that probiotic, paraprobotic and 20 posbiotic were able to decrease the neutrophil inflammatory infiltrate and gene expression of the pro-inflammatory cytokine Il12p40, in addition to increasing the relative gene expression of Claudine (Cldn2). Supplementation with probiotics and paraprobotics were also able to negatively regulate the relative gene expression of Tnf and positively that of ll10. However, only the administration of probiotics was able to decrease the recruitment of eosinophils. 25 Similarly, only administration of probiotics was able to prevent increased inflammatory infiltrate of eosinophils, and only paraprobiotics prevents the increase of Il1b and the shortening of villus. Based on these results, the present study demonstrated that CIDCA 133 probiotic, paraprobiotic and postbiotic were able to partially attenuate the inflammatory and histopathological parameters of the intestinal mucositis induces by antineoplastic 5-FU, 30 however, new studies should be conducted to elucidate the mechanisms related to the beneficial effects found in the present study.
publishDate 2021
dc.date.none.fl_str_mv 2021-04-27T20:42:54Z
2021-04-27T20:42:54Z
2021-03-31
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/35844
url http://hdl.handle.net/1843/35844
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
Programa de Pós-Graduação em Genética
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
Programa de Pós-Graduação em Genética
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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