Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Machado, Sandro Max Pinto
Orientador(a): Duarte, Antoniella Souza Gomes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
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/77640
Resumo: Inflammatory bowel diseases (IBD) represent a group of chronic idiopathic inflammatory intestinal disorders. The etiology of these diseases is not fully understood, but there is a relationship with genetic, environmental factors, and alterations in the intestinal microbiota. However, the two main categories of IBD are Crohn's disease (CD) and ulcerative colitis (UC), which have overlapping clinical and pathological features and some distinct characteristics. CD can affect the entire gastrointestinal tract and exhibits transmural infiltration and elevated levels of tumor necrosis factor-alpha (TNF-α). It affects the layers surrounding the hollow organs of the intestinal digestive tube, affecting the terminal ileum, cecum, colon, and perianal region, often resulting in granulomas and the development of fistulas. IBDs are incurable, and treatments aim only to control symptoms. Alterations in intestinal mucosal permeability are biological and physiological complications caused by CD. The epithelial cells that form the barrier between the body and the intraluminal microenvironment are highly selective. However, during inflammation, macromolecules such as bacterial or fecal antigens may flow in quantities above normal. The Ministry of Health, through the National Policy of Integrative and Complementary Practices (NPICP), encourages the provision of Acupuncture, Homeopathy, Phytotherapy, Hydrotherapy, and Anthroposophic Medicine in the Unified Health System (SUS). Seeking the development of new strategies and therapeutic agents is essential for the treatment of both pathologies. Naringin is a chemical phytotherapeutic compound that belongs to flavones, known as 4, 5, 7-trihydroxy-flavanone-7-rhamnoglucoside. It was discovered by De Vry in 1857 in Citrus paradisi (Grapefruit) flowers. Naringin presents pharmacological properties such as anti-osteoporotic, anticancer, antiapoptotic, and anti-inflammatory activities, as well as acting on metabolic syndrome and central nervous system disorders, including neurological disorders. It is a substance with great pharmacological potential. In this study, we induced CD in animals. The animals were previously anesthetized intraperitoneally (i.p) with ketamine (60mg/kg) and xylazine (5mg/kg) and challenged with acetic acid (10mg/animal) for three consecutive days. Additional groups received acetic acid (10mg/animal) plus naringin at concentrations of 200 mg/kg, 100 mg/kg, and 50 mg/kg. After the induction protocol of CD by acetic acid, the animals were euthanized 6 hours after the last application. Colon segments of mice were collected for the analysis of the following parameters: macroscopy, microscopy, GSH, MDA, TNF-α, and IL-6. Naringin extract significantly reduced acetic acidinduced macroscopic and microscopic lesions. Naringin at a concentration of 100 mg/kg prevented GSH depletion, reduced MDA levels, and decreased neutrophil infiltration. Furthermore, naringin reduced levels of pro-inflammatory cytokines TNF-α and IL-1β, reversing the effect of acetic acid. Therefore, naringin demonstrated an anti-inflammatory and antioxidant effect in the Crohn's disease model.
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spelling Machado, Sandro Max PintoMartins, Dainesy SantosDuarte, Antoniella Souza Gomes2024-08-12T17:54:53Z2024-08-12T17:54:53Z2023MACHADO, Sandro Max Pinto. Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos. 2024. 82 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77640. Acesso em: 12 ago. 2024.http://repositorio.ufc.br/handle/riufc/77640Inflammatory bowel diseases (IBD) represent a group of chronic idiopathic inflammatory intestinal disorders. The etiology of these diseases is not fully understood, but there is a relationship with genetic, environmental factors, and alterations in the intestinal microbiota. However, the two main categories of IBD are Crohn's disease (CD) and ulcerative colitis (UC), which have overlapping clinical and pathological features and some distinct characteristics. CD can affect the entire gastrointestinal tract and exhibits transmural infiltration and elevated levels of tumor necrosis factor-alpha (TNF-α). It affects the layers surrounding the hollow organs of the intestinal digestive tube, affecting the terminal ileum, cecum, colon, and perianal region, often resulting in granulomas and the development of fistulas. IBDs are incurable, and treatments aim only to control symptoms. Alterations in intestinal mucosal permeability are biological and physiological complications caused by CD. The epithelial cells that form the barrier between the body and the intraluminal microenvironment are highly selective. However, during inflammation, macromolecules such as bacterial or fecal antigens may flow in quantities above normal. The Ministry of Health, through the National Policy of Integrative and Complementary Practices (NPICP), encourages the provision of Acupuncture, Homeopathy, Phytotherapy, Hydrotherapy, and Anthroposophic Medicine in the Unified Health System (SUS). Seeking the development of new strategies and therapeutic agents is essential for the treatment of both pathologies. Naringin is a chemical phytotherapeutic compound that belongs to flavones, known as 4, 5, 7-trihydroxy-flavanone-7-rhamnoglucoside. It was discovered by De Vry in 1857 in Citrus paradisi (Grapefruit) flowers. Naringin presents pharmacological properties such as anti-osteoporotic, anticancer, antiapoptotic, and anti-inflammatory activities, as well as acting on metabolic syndrome and central nervous system disorders, including neurological disorders. It is a substance with great pharmacological potential. In this study, we induced CD in animals. The animals were previously anesthetized intraperitoneally (i.p) with ketamine (60mg/kg) and xylazine (5mg/kg) and challenged with acetic acid (10mg/animal) for three consecutive days. Additional groups received acetic acid (10mg/animal) plus naringin at concentrations of 200 mg/kg, 100 mg/kg, and 50 mg/kg. After the induction protocol of CD by acetic acid, the animals were euthanized 6 hours after the last application. Colon segments of mice were collected for the analysis of the following parameters: macroscopy, microscopy, GSH, MDA, TNF-α, and IL-6. Naringin extract significantly reduced acetic acidinduced macroscopic and microscopic lesions. Naringin at a concentration of 100 mg/kg prevented GSH depletion, reduced MDA levels, and decreased neutrophil infiltration. Furthermore, naringin reduced levels of pro-inflammatory cytokines TNF-α and IL-1β, reversing the effect of acetic acid. Therefore, naringin demonstrated an anti-inflammatory and antioxidant effect in the Crohn's disease model.As doenças inflamatórias intestinais (DII) representam um grupo de afecções intestinais inflamatórias crônicas idiopáticas. A etiologia dessas doenças não é completamente conhecida, mas há uma relação com fatores genéticos, ambientais e alterações na microbiota intestinal. Entretanto, as duas principais categorias de DII são a doença de Crohn (DC) e a retocolite ulcerativa (UC), que apresentam características clínico-patológicas sobrepostas e outras bem diferentes. A DC pode acometer todo o trato gastrointestinal e apresenta infiltração transmural e níveis elevados do fator de necrose tumoral alfa (TNF-α). Ela afeta as camadas que circundam os órgãos ocos do tubo digestório intestinal, afetando a região terminal do íleo, ceco, cólon e região perianal, muitas vezes resultando em granulomas e o desenvolvimento de fístulas. As DII não têm cura, e os tratamentos visam apenas ao controle dos sintomas. As alterações na permeabilidade da mucosa intestinal são complicações biológicas e fisiológicas causadas pela DC. As células epiteliais que formam a barreira entre o corpo e o microambiente intraluminal são altamente seletivas. No entanto, durante a inflamação, macromoléculas como antígenos bacterianos ou fecais podem fluir em quantidade acima do normal. O Ministério da Saúde, por meio da Política Nacional de Práticas Integrativas e Complementares (PNPIC), incentiva a oferta de Acupuntura, Homeopatia, Fitoterapia, Hidroterapia e Medicina Antroposófica no Sistema Único de Saúde (SUS). Buscar o desenvolvimento de novas estratégias e agentes terapêuticos é essencial para o tratamento de ambas as patologias. A Naringina é um composto fitoterápico químico que pertence às flavonas, conhecida como 4, 5, 7-trihidroxi-flavanona-7-ramnoglucósido. Foi descoberta por De Vry em 1857, em flores de Citrus paradisi (Toranja). A Naringina apresenta propriedades farmacológicas, como atividades antiosteoporóticas, anticâncer, anti-apoptóticas e anti-inflamatórias, além de atuar na síndrome metabólica e em distúrbios do sistema nervoso central, incluindo distúrbios neurológicos. É uma substância com grande potencial farmacológico. Neste estudo, induzimos a DC em animais. Os animais foram previamente anestesiados por via intraperitoneal (i.p) com quetamina (60mg/kg) e xilazina (5mg/kg) e desafiados com ácido acético (10mg/animal) durante três dias consecutivos. Grupos adicionais receberam ácido acético (AA 8%)(10mg/animal) mais Naringina nas concentrações de 200 mg/kg, 100 mg/kg e 50 mg/kg. Após o protocolo de indução de DC por ácido acético (AA 8%), os animais foram eutanasiados 12 horas após a última aplicação. Os segmentos de cólon dos camundongos foram coletados para a análise dos seguintes parâmetros: macroscopia, microscopia, GSH, MDA, TNF-α e IL-1β. O extrato de Naringina reduziu significativamente a lesão macroscópica e microscópica induzida pelo ácido acético (AA 8%). Verificamos neste estudo que a Naringina na concentração de 100 mg/kg preveniu a depleção nos níveis de GSH, reduziu os níveis de MDA. Além disso, a Naringina reduziu os níveis de citocinas próinflamatórias TNF-α e IL-1β, revertendo o efeito do ácido acético. Portanto, a Naringina demonstrou um efeito anti-inflamatório e antioxidante no modelo de Doença de Crohn.Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisDoença de CrohnAntioxidantesFlavonóidesCrohn DiseaseAntioxidantsFlavonoidsCNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/0570197301056219http://lattes.cnpq.br/1674590681546363http://lattes.cnpq.br/7849359138303591ORIGINAL2024_dis_smpmachado.pdf2024_dis_smpmachado.pdfapplication/pdf2303041http://repositorio.ufc.br/bitstream/riufc/77640/1/2024_dis_smpmachado.pdf3f15492a13a82c8553ef36af29bbe557MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/77640/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54riufc/776402024-08-12 14:55:31.984oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-08-12T17:55:31Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
title Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
spellingShingle Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
Machado, Sandro Max Pinto
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
Doença de Crohn
Antioxidantes
Flavonóides
Crohn Disease
Antioxidants
Flavonoids
title_short Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
title_full Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
title_fullStr Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
title_full_unstemmed Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
title_sort Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos
author Machado, Sandro Max Pinto
author_facet Machado, Sandro Max Pinto
author_role author
dc.contributor.co-advisor.none.fl_str_mv Martins, Dainesy Santos
dc.contributor.author.fl_str_mv Machado, Sandro Max Pinto
dc.contributor.advisor1.fl_str_mv Duarte, Antoniella Souza Gomes
contributor_str_mv Duarte, Antoniella Souza Gomes
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
topic CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
Doença de Crohn
Antioxidantes
Flavonóides
Crohn Disease
Antioxidants
Flavonoids
dc.subject.ptbr.pt_BR.fl_str_mv Doença de Crohn
Antioxidantes
Flavonóides
dc.subject.en.pt_BR.fl_str_mv Crohn Disease
Antioxidants
Flavonoids
description Inflammatory bowel diseases (IBD) represent a group of chronic idiopathic inflammatory intestinal disorders. The etiology of these diseases is not fully understood, but there is a relationship with genetic, environmental factors, and alterations in the intestinal microbiota. However, the two main categories of IBD are Crohn's disease (CD) and ulcerative colitis (UC), which have overlapping clinical and pathological features and some distinct characteristics. CD can affect the entire gastrointestinal tract and exhibits transmural infiltration and elevated levels of tumor necrosis factor-alpha (TNF-α). It affects the layers surrounding the hollow organs of the intestinal digestive tube, affecting the terminal ileum, cecum, colon, and perianal region, often resulting in granulomas and the development of fistulas. IBDs are incurable, and treatments aim only to control symptoms. Alterations in intestinal mucosal permeability are biological and physiological complications caused by CD. The epithelial cells that form the barrier between the body and the intraluminal microenvironment are highly selective. However, during inflammation, macromolecules such as bacterial or fecal antigens may flow in quantities above normal. The Ministry of Health, through the National Policy of Integrative and Complementary Practices (NPICP), encourages the provision of Acupuncture, Homeopathy, Phytotherapy, Hydrotherapy, and Anthroposophic Medicine in the Unified Health System (SUS). Seeking the development of new strategies and therapeutic agents is essential for the treatment of both pathologies. Naringin is a chemical phytotherapeutic compound that belongs to flavones, known as 4, 5, 7-trihydroxy-flavanone-7-rhamnoglucoside. It was discovered by De Vry in 1857 in Citrus paradisi (Grapefruit) flowers. Naringin presents pharmacological properties such as anti-osteoporotic, anticancer, antiapoptotic, and anti-inflammatory activities, as well as acting on metabolic syndrome and central nervous system disorders, including neurological disorders. It is a substance with great pharmacological potential. In this study, we induced CD in animals. The animals were previously anesthetized intraperitoneally (i.p) with ketamine (60mg/kg) and xylazine (5mg/kg) and challenged with acetic acid (10mg/animal) for three consecutive days. Additional groups received acetic acid (10mg/animal) plus naringin at concentrations of 200 mg/kg, 100 mg/kg, and 50 mg/kg. After the induction protocol of CD by acetic acid, the animals were euthanized 6 hours after the last application. Colon segments of mice were collected for the analysis of the following parameters: macroscopy, microscopy, GSH, MDA, TNF-α, and IL-6. Naringin extract significantly reduced acetic acidinduced macroscopic and microscopic lesions. Naringin at a concentration of 100 mg/kg prevented GSH depletion, reduced MDA levels, and decreased neutrophil infiltration. Furthermore, naringin reduced levels of pro-inflammatory cytokines TNF-α and IL-1β, reversing the effect of acetic acid. Therefore, naringin demonstrated an anti-inflammatory and antioxidant effect in the Crohn's disease model.
publishDate 2023
dc.date.issued.fl_str_mv 2023
dc.date.accessioned.fl_str_mv 2024-08-12T17:54:53Z
dc.date.available.fl_str_mv 2024-08-12T17:54:53Z
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dc.identifier.citation.fl_str_mv MACHADO, Sandro Max Pinto. Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos. 2024. 82 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77640. Acesso em: 12 ago. 2024.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/77640
identifier_str_mv MACHADO, Sandro Max Pinto. Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos. 2024. 82 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77640. Acesso em: 12 ago. 2024.
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