Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência
Ano de defesa: | 2021 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/25023 |
Resumo: | Introduction: Brazil has shown an accelerated aging process when compared to other countries in the world, a fact that directly impacts health and social care systems, as biological aging is associated with dysfunctions that increase the risk of dependence, non-communicable chronic diseases (NCCDs), institutionalization, hospitalization and death. In addition, it reduces the efficiency of the immune response against infection by pathogens, a situation observed in the Covid-19 pandemic, in which the elderly people were the most affected. Epidemiological, clinical and experimental evidence suggests that biological aging could be modulated by environmental factors such as diet, which seems to be able to mitigate relevant physiological changes. Objectives: In this sense, this study aimed to evaluate the genomic effect of aqueous extracts of coffee, black and green teas, yerba mate and guarana in the modulation of oxidative and inflammatory markers. The first study analyzed the inflammatory modulation of non-activated peripheral blood mononuclear cells (na-PBMCs), yeast-activated human neutrophils, and Eisenia fetida earthworm granulocytic coelomocytes. The second study involved two separate protocols. The first one evaluated the inflammatory activation of PBMCs obtained from healthy individuals before and after ingesting 100 mL of each drink, by modulation of reactive oxygen species (ROS). The second protocol involved an in vitro analysis of caffeinated extracts and isolated bioactive molecules caffeine (Caf), theobromine (The) and catechin (Cat) in the modulation of antioxidant enzymes genes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Results: The results of the first study are published in the journal Food and Chemical Toxicology. Immunoassays performed in human PBMCs cultured for 24 hours showed that all extracts decreased the levels of the pro-inflammatory cytokines IL-1β, IL 6, TNF-α and IFN-γ, and increased the levels of the anti-inflammatory cytokine IL-10, in addition to induce an overexpression of their genes. An additional assay, in which human neutrophils with and without treatment to the extracts were exposed to inactivated yeasts, showed that there was an increase in the production of neutrophil extracellular traps (NETs). The analysis of the inflammatory response triggered in earthworms treated with the extracts and exposed to inactivated yeasts corroborated the hypothesis that these beverages improve the immune response in the presence of pathogens, being, however, distinct for each extract, with special emphasis on yerba mate. The second study was submitted to the journal Nutrition and analyzed PBMC cultures before and after the ingestion of extracts, demonstrating a decrease in viability and in nitric oxide (NO) levels after ingestion. The extracts exhibited high similarity in the regulation of antioxidant genes, decreasing their expression. Conclusions: The set of results suggests that caffeinated beverages share bioactive components in their chemical matrix, and have similar action, modulating low-grade chronic inflammatory processes and increasing the competence of acute inflammation triggered by pathogens. Thus, it seems that caffeinated beverages may attenuate immunossenescence processes associated with the dysfunctions and NCCDs prevalent in biological aging. |
id |
UFSM_682215c7d2bd5c345d9182030259b5b8 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/25023 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
spelling |
2022-06-22T20:05:30Z2022-06-22T20:05:30Z2021-12-10http://repositorio.ufsm.br/handle/1/25023Introduction: Brazil has shown an accelerated aging process when compared to other countries in the world, a fact that directly impacts health and social care systems, as biological aging is associated with dysfunctions that increase the risk of dependence, non-communicable chronic diseases (NCCDs), institutionalization, hospitalization and death. In addition, it reduces the efficiency of the immune response against infection by pathogens, a situation observed in the Covid-19 pandemic, in which the elderly people were the most affected. Epidemiological, clinical and experimental evidence suggests that biological aging could be modulated by environmental factors such as diet, which seems to be able to mitigate relevant physiological changes. Objectives: In this sense, this study aimed to evaluate the genomic effect of aqueous extracts of coffee, black and green teas, yerba mate and guarana in the modulation of oxidative and inflammatory markers. The first study analyzed the inflammatory modulation of non-activated peripheral blood mononuclear cells (na-PBMCs), yeast-activated human neutrophils, and Eisenia fetida earthworm granulocytic coelomocytes. The second study involved two separate protocols. The first one evaluated the inflammatory activation of PBMCs obtained from healthy individuals before and after ingesting 100 mL of each drink, by modulation of reactive oxygen species (ROS). The second protocol involved an in vitro analysis of caffeinated extracts and isolated bioactive molecules caffeine (Caf), theobromine (The) and catechin (Cat) in the modulation of antioxidant enzymes genes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Results: The results of the first study are published in the journal Food and Chemical Toxicology. Immunoassays performed in human PBMCs cultured for 24 hours showed that all extracts decreased the levels of the pro-inflammatory cytokines IL-1β, IL 6, TNF-α and IFN-γ, and increased the levels of the anti-inflammatory cytokine IL-10, in addition to induce an overexpression of their genes. An additional assay, in which human neutrophils with and without treatment to the extracts were exposed to inactivated yeasts, showed that there was an increase in the production of neutrophil extracellular traps (NETs). The analysis of the inflammatory response triggered in earthworms treated with the extracts and exposed to inactivated yeasts corroborated the hypothesis that these beverages improve the immune response in the presence of pathogens, being, however, distinct for each extract, with special emphasis on yerba mate. The second study was submitted to the journal Nutrition and analyzed PBMC cultures before and after the ingestion of extracts, demonstrating a decrease in viability and in nitric oxide (NO) levels after ingestion. The extracts exhibited high similarity in the regulation of antioxidant genes, decreasing their expression. Conclusions: The set of results suggests that caffeinated beverages share bioactive components in their chemical matrix, and have similar action, modulating low-grade chronic inflammatory processes and increasing the competence of acute inflammation triggered by pathogens. Thus, it seems that caffeinated beverages may attenuate immunossenescence processes associated with the dysfunctions and NCCDs prevalent in biological aging.Introdução: O Brasil tem apresentado um envelhecimento populacional acelerado quando comparado com outros países do mundo, fato que impacta diretamente os sistemas de saúde e assistência social, pois o envelhecimento biológico está associado a disfunções que aumentam o risco de dependência, de doenças crônicas não transmissíveis, institucionalização, hospitalização e morte. Além disso, diminui a eficiência da resposta imune frente a infecção por patógenos, situação observada na pandemia Covid-19, na qual os idosos foram os mais afetados. Evidências epidemiológicas, clínicas e experimentais sugerem que o envelhecimento biológico pode ser modulado por fatores ambientais como a dieta, que parece ser capaz de atenuar alterações fisiológicas relevantes. Objetivos: Neste sentido, este estudo buscou avaliar o efeito genômico dos extratos aquosos de café, chás preto e verde, erva-mate e guaraná na modulação de marcadores oxidativos e inflamatórios. O primeiro estudo analisou a modulação inflamatória de células mononucleares do sangue periférico não ativadas (CMSPs-na), neutrófilos humanos ativados por levedura e celomócitos granulocíticos da minhoca E. fetida. O segundo estudo envolveu dois protocolos distintos. O primeiro avaliou a ativação inflamatória de CMSPs obtidas de indivíduos saudáveis antes e após a ingestão de 100mL de cada bebida, via modulação de espécies reativas (ERs). O segundo protocolo envolveu uma análise in vitro dos extratos cafeinados e das moléculas bioativas isoladas cafeína (Caf), teobromina (The) e catequina (Cat) na modulação dos genes das enzimas antioxidantes superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPX). Resultados: Os resultados do primeiro estudo estão publicados no periódico Food and Chemical Toxicology. Imunoensaios realizados em CMSPs humanas cultivadas por 24hs mostraram que todos os extratos diminuíram os níveis das citocinas pró-inflamatórias IL-1β, IL 6, TNF-α e IFN-γ, e aumentaram os níveis da anti-inflamatória, IL-10, além de induzir uma super expressão dos seus genes. Um ensaio adicional, no qual neutrófilos humanos com e sem exposição aos extratos foram expostos a leveduras inativadas, mostrou que houve aumento na produção de armadilhas extracelulares (NETs). A análise da resposta inflamatória desencadeada em minhocas tratadas com os extratos e expostas a leveduras inativadas corroborou a hipótese de que estas bebidas melhoram a resposta imunológica na presença de patógenos sendo, porém, distinta para cada extrato, com destaque especial para a erva-mate. O segundo estudo foi submetido ao periódico Nutrition e analisou culturas de CMSPs antes e após a ingestão dos extratos, demonstrando diminuição da viabilidade e dos níveis de óxido nítrico (ON) após a ingestão. Os extratos exibiram alta similaridade na regulação dos genes antioxidantes, diminuindo a expressão dos mesmos. Conclusões: O conjunto dos resultados sugere que bebidas cafeinadas compartilham componentes bioativos nas suas matrizes químicas, e que os mesmos possuem similaridade de ação, modulando processos inflamatórios crônicos de baixo grau e aumentando a competência da inflamação aguda desencadeada por agentes patogênicos. Assim, parece que bebidas cafeinadas são atenuadoras de processos de imunossenescência associados as disfunções e DCNTs prevalentes no envelhecimento biológico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEnvelhecimentoInflamaçãoImunossenescênciaAgingInflammationImmunosenescenceCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAEfeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescênciainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCruz, Ivana Beatrice Mânica dahttp://lattes.cnpq.br/3426369324110716Nascimento, Patrícia Severo doEmanuelli, TatianaBagatini, Margarete DulcePiccoli, Jacqueline da Costa Escobarhttp://lattes.cnpq.br/7457800138518629Alves, Audrei de Oliveira2010000000006000b5fcfe0-b017-4163-80e2-17c110fbcf012012bf69-3f10-419c-bef6-4e0fe9b894439a9a61b1-bfc2-4d41-b8c7-ce9a4491aaa07370992c-57db-4a0a-ba21-f4364486c5ec273abd78-5b59-457d-b813-1eec64454b6a35312a11-10e0-44d0-98ee-966e60ef43dfreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/25023/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/25023/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALTES_PPGFARMACOLOGIA_2021_ALVES_AUDREI.pdfTES_PPGFARMACOLOGIA_2021_ALVES_AUDREI.pdfTese de Doutoradoapplication/pdf2394615http://repositorio.ufsm.br/bitstream/1/25023/1/TES_PPGFARMACOLOGIA_2021_ALVES_AUDREI.pdf6e5fe960095bba1cdfcd52a1cea46598MD511/250232022-07-12 10:28:11.45oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-07-12T13:28:11Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
title |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
spellingShingle |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência Alves, Audrei de Oliveira Envelhecimento Inflamação Imunossenescência Aging Inflammation Immunosenescence CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
title_full |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
title_fullStr |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
title_full_unstemmed |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
title_sort |
Efeito genômico de bebidas ricas em cafeína e catequinas na modulação de marcadores oxidativos e inflamatórios associados a imunossenescência |
author |
Alves, Audrei de Oliveira |
author_facet |
Alves, Audrei de Oliveira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cruz, Ivana Beatrice Mânica da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3426369324110716 |
dc.contributor.referee1.fl_str_mv |
Nascimento, Patrícia Severo do |
dc.contributor.referee2.fl_str_mv |
Emanuelli, Tatiana |
dc.contributor.referee3.fl_str_mv |
Bagatini, Margarete Dulce |
dc.contributor.referee4.fl_str_mv |
Piccoli, Jacqueline da Costa Escobar |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7457800138518629 |
dc.contributor.author.fl_str_mv |
Alves, Audrei de Oliveira |
contributor_str_mv |
Cruz, Ivana Beatrice Mânica da Nascimento, Patrícia Severo do Emanuelli, Tatiana Bagatini, Margarete Dulce Piccoli, Jacqueline da Costa Escobar |
dc.subject.por.fl_str_mv |
Envelhecimento Inflamação Imunossenescência |
topic |
Envelhecimento Inflamação Imunossenescência Aging Inflammation Immunosenescence CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Aging Inflammation Immunosenescence |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Introduction: Brazil has shown an accelerated aging process when compared to other countries in the world, a fact that directly impacts health and social care systems, as biological aging is associated with dysfunctions that increase the risk of dependence, non-communicable chronic diseases (NCCDs), institutionalization, hospitalization and death. In addition, it reduces the efficiency of the immune response against infection by pathogens, a situation observed in the Covid-19 pandemic, in which the elderly people were the most affected. Epidemiological, clinical and experimental evidence suggests that biological aging could be modulated by environmental factors such as diet, which seems to be able to mitigate relevant physiological changes. Objectives: In this sense, this study aimed to evaluate the genomic effect of aqueous extracts of coffee, black and green teas, yerba mate and guarana in the modulation of oxidative and inflammatory markers. The first study analyzed the inflammatory modulation of non-activated peripheral blood mononuclear cells (na-PBMCs), yeast-activated human neutrophils, and Eisenia fetida earthworm granulocytic coelomocytes. The second study involved two separate protocols. The first one evaluated the inflammatory activation of PBMCs obtained from healthy individuals before and after ingesting 100 mL of each drink, by modulation of reactive oxygen species (ROS). The second protocol involved an in vitro analysis of caffeinated extracts and isolated bioactive molecules caffeine (Caf), theobromine (The) and catechin (Cat) in the modulation of antioxidant enzymes genes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Results: The results of the first study are published in the journal Food and Chemical Toxicology. Immunoassays performed in human PBMCs cultured for 24 hours showed that all extracts decreased the levels of the pro-inflammatory cytokines IL-1β, IL 6, TNF-α and IFN-γ, and increased the levels of the anti-inflammatory cytokine IL-10, in addition to induce an overexpression of their genes. An additional assay, in which human neutrophils with and without treatment to the extracts were exposed to inactivated yeasts, showed that there was an increase in the production of neutrophil extracellular traps (NETs). The analysis of the inflammatory response triggered in earthworms treated with the extracts and exposed to inactivated yeasts corroborated the hypothesis that these beverages improve the immune response in the presence of pathogens, being, however, distinct for each extract, with special emphasis on yerba mate. The second study was submitted to the journal Nutrition and analyzed PBMC cultures before and after the ingestion of extracts, demonstrating a decrease in viability and in nitric oxide (NO) levels after ingestion. The extracts exhibited high similarity in the regulation of antioxidant genes, decreasing their expression. Conclusions: The set of results suggests that caffeinated beverages share bioactive components in their chemical matrix, and have similar action, modulating low-grade chronic inflammatory processes and increasing the competence of acute inflammation triggered by pathogens. Thus, it seems that caffeinated beverages may attenuate immunossenescence processes associated with the dysfunctions and NCCDs prevalent in biological aging. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-12-10 |
dc.date.accessioned.fl_str_mv |
2022-06-22T20:05:30Z |
dc.date.available.fl_str_mv |
2022-06-22T20:05:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/25023 |
url |
http://repositorio.ufsm.br/handle/1/25023 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
0b5fcfe0-b017-4163-80e2-17c110fbcf01 2012bf69-3f10-419c-bef6-4e0fe9b89443 9a9a61b1-bfc2-4d41-b8c7-ce9a4491aaa0 7370992c-57db-4a0a-ba21-f4364486c5ec 273abd78-5b59-457d-b813-1eec64454b6a 35312a11-10e0-44d0-98ee-966e60ef43df |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/25023/2/license_rdf http://repositorio.ufsm.br/bitstream/1/25023/3/license.txt http://repositorio.ufsm.br/bitstream/1/25023/1/TES_PPGFARMACOLOGIA_2021_ALVES_AUDREI.pdf |
bitstream.checksum.fl_str_mv |
4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df 6e5fe960095bba1cdfcd52a1cea46598 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1793240160272384000 |