Efeito do tratamento do acetato na exacerbação da inflamação alérgica pulmonar em camundongos ovariectomizados
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Data
2024-03-12
Autores
Umana, Evelyn Roxana Perez [UNIFESP]
Orientadores
Ferreira, Caroline Marcantonio [UNIFESP]
Tipo
Tese de doutorado
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Objetivo: Avaliar o papel do tratamento preventivo e terapêutico com acetato, um ácido graxo de cadeia curta (AGCC), e potenciais alterações intestinais durante a exacerbação da inflamação alérgica pulmonar em animais alérgicos ovariectomizados e redesafiados. Métodos: Camundongos fêmeas da linhagem BALB/c, com idades entre 6 e 7 semanas foram utilizadas no estudo. No tratamento preventivo, os animais receberam acetato (1g/kg) por via intraperitoneal (IP) em dias alternados, 15 dias antes das sensibilizações, até um dia antes do início dos desafios. O tratamento terapêutico foi administrado em dias alternados após a ovariectomia, utilizando a mesma dose e via de administração até um dia antes da eutanásia. A indução da inflamação alérgica pulmonar ocorreu com duas sensibilizações nos dias 0 e 14, utilizando uma solução de [OVA (30µg+Al (OH)3 (2mg)] via IP. Os desafios foram realizados expondo os animais a uma solução de 1% de OVA/PBS por nebulização nos dias 21, 22, 23 e 24. A ovariectomia foi realizada no 34º dia. Os camundongos foram reexpostos ao OVA nos dias 44, 45, 46 e 47. A eutanásia foi realizada 24 horas após o último desafio.
Resultados: O tratamento preventivo resultou na redução do número de células totais, eosinófilos, IgE e da citocina IL-5, além de promover o aumento de células T reguladoras. As análises histológicas pulmonares mostraram uma diminuição na produção de muco neutro e de anéis inflamatórios peribronquiais e perivasculares. No intestino, observou-se uma restauração dos níveis de expressão gênica de MUCINA 2 e OCLUDINA. Por outro lado, o tratamento terapêutico não teve efeito sobre a inflamação alérgica pulmonar. Conclusões: O tratamento preventivo demostrou eficácia na redução da exacerbação da inflamação alérgica pulmonar. Além disso, restaurou os níveis das expressões genicas de MUCINA 2 e da OCLUDINA a valores similares dos grupos basais no colón intestinal. Palavras-chaves: acetato, ácidos graxos de cadeia curta, inflamação alérgica pulmonar, asma e hormônios sexuais femininos.
Objective: To evaluate the role of preventive and therapeutic treatment with acetate, a short-chain fatty acid (SCFA), and potential intestinal alterations during the exacerbation of pulmonary allergic inflammation in ovariectomized and rechallenged allergic animals. Methods: Female BALB/c mice, aged between 6 and 7 weeks, were utilized in the study. In the preventive treatment, animals received acetate (1g/kg) intraperitoneally (IP) on alternate days, starting 15 days before sensitization, until one day before the onset of challenges. Therapeutic treatment was administered on alternate days after ovariectomy, using the same dose and route of administration until one day before euthanasia. Pulmonary allergic inflammation was induced with two sensitizations on days 0 and 14, using a solution of [OVA (30µg+Al (OH)3 (2mg)] via IP. Challenges were performed by exposing animals to a 1% OVA/PBS solution by nebulization on days 21, 22, 23, and 24. Ovariectomy was conducted on the 34th day. Mice were re-exposed to OVA on days 44, 45, 46, and 47. The euthanasia was performed 24 hours after the last challenge. Results: Preventive treatment resulted in a reduction in the total number of cells, eosinophils, IgE, and IL-5 cytokine, as well as an increase in regulatory T cells. Pulmonary histological analyses showed a decrease in neutral mucus production and peribronchial and perivascular inflammatory rings. In the intestine, restoration of MUCINA 2 and OCLUDINA gene expression levels was observed. Conversely, therapeutic treatment had no effect on pulmonary allergic inflammation. Conclusions: Preventive treatment demonstrated efficacy in reducing the exacerbation of pulmonary allergic inflammation. Additionally, it restored the gene expression levels of MUCINA 2 and OCLUDINA to values similar to those of the basal groups in the intestinal colon.
Objective: To evaluate the role of preventive and therapeutic treatment with acetate, a short-chain fatty acid (SCFA), and potential intestinal alterations during the exacerbation of pulmonary allergic inflammation in ovariectomized and rechallenged allergic animals. Methods: Female BALB/c mice, aged between 6 and 7 weeks, were utilized in the study. In the preventive treatment, animals received acetate (1g/kg) intraperitoneally (IP) on alternate days, starting 15 days before sensitization, until one day before the onset of challenges. Therapeutic treatment was administered on alternate days after ovariectomy, using the same dose and route of administration until one day before euthanasia. Pulmonary allergic inflammation was induced with two sensitizations on days 0 and 14, using a solution of [OVA (30µg+Al (OH)3 (2mg)] via IP. Challenges were performed by exposing animals to a 1% OVA/PBS solution by nebulization on days 21, 22, 23, and 24. Ovariectomy was conducted on the 34th day. Mice were re-exposed to OVA on days 44, 45, 46, and 47. The euthanasia was performed 24 hours after the last challenge. Results: Preventive treatment resulted in a reduction in the total number of cells, eosinophils, IgE, and IL-5 cytokine, as well as an increase in regulatory T cells. Pulmonary histological analyses showed a decrease in neutral mucus production and peribronchial and perivascular inflammatory rings. In the intestine, restoration of MUCINA 2 and OCLUDINA gene expression levels was observed. Conversely, therapeutic treatment had no effect on pulmonary allergic inflammation. Conclusions: Preventive treatment demonstrated efficacy in reducing the exacerbation of pulmonary allergic inflammation. Additionally, it restored the gene expression levels of MUCINA 2 and OCLUDINA to values similar to those of the basal groups in the intestinal colon.
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Citação
UMANA, Evelyn Roxana Perez. Efeito do tratamento do acetato na exacerbação da inflamação alérgica pulmonar em camundongos ovariectomizado. 2024. 81 f. Tese (Doutorado em Patologia) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo. 2024.