Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação

Detalhes bibliográficos
Autor(a) principal: Ferreira, Sarah Rebeca Dantas
Data de Publicação: 2022
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/26124
Resumo: Obesity and asthma combined result in an asthma phenotype with more severe symptoms and reduced response to corticosteroid treatment; however, the exact mechanism responsible for these changes remains unclear. In this context, a promising drug is Hibiscus sabdariffa L., popularly known as “hibiscus”, which has already shown anti-obesity activity and spasmolytic action in guinea pig trachea. Thus, the aim of this work was to standardize and implement a animal model of obesity-exacerbated asthma employing a high glycemic index diet (HGLI) and ovalbumin (OVA), characterizing in vivo and in vitro, morphologically, and functionally, the alterations induced by the combined diseases, evaluating also whether treatment with hibiscus would prevent the changes induced by them, characterizing its mechanism of action. Wistar rats (n = 5-6) were divided into control (CG), obese (OG), asthmatic (AG), obese asthmatic (OAG), obese asthmatic dexamethasone (OADEXAG), obese asthmatic hibiscus 250 mg/kg (OAH250G), obese asthmatic hibiscus 500 mg/kg (OAH500G) and obese asthmatic hibiscus 1000 mg/kg (OAH1000G). The experimental protocols were approved by CEUA/UFPB (5975030920). It was observed that obesity-related parameters, such as body weight, waist circumference, body mass index (BMI), and adiposity index were increased in OG and OAG. Treatment with dexamethasone caused weight loss compared to OAG, however, it did not reverse the increase in the other observed parameters. Hibiscus at doses of 500 and 1000 mg/kg prevented the increase in weight, BMI, abdominal circumference and adiposity. Histologically, an increase in the diameter of the adipose tissue in the animals fed with HGLI (OG and OAG) has been observed with prevention of these in OADEXAG and OAH500G. To characterize the implantation of asthma, lung function was measured using the spirometry technique (days 1, 12 and 21 of asthma induction) and no change in respiratory rate was observed, although a reduction in tidal volume and volume-minute on the 21st in AG and OAG has been reached, and this change was not reversed in OADEXAG and OAH500G. Lung histology demonstrated exacerbation of peribronchovascular inflammation in OAG compared to isolated diseases, as well as smooth muscle hypertrophy and extracellular matrix remodeling compared to CG. Functionally, the trachea was used to assess contractile and relaxing reactivity and elucidate the mechanism of action. Animals that were previously sensitized with OVA showed a contractile response to the allergen (AG and OAG), which was even greater in OAG and without reversion in OADEXAG or OAH500G. The electromechanical or histamine-induced contraction do not seemed to be involved in the diseases, with the exception of AG, which showed an increase in contractile efficacy with no change in potency against histamine. Otherwise, in the cumulative concentration-response curve to carbachol (CCh) has been observed an increase in contractile efficacy in OG, AG and OAG, with OAG being even greater than AG and with no change in potency between groups. This increase was not altered in OAH250G, however OAH500G and OAH100G prevented it, without changing the potency. On the other hand, the relaxing reactivity to nifedipine and aminophylline were not altered between the groups. While isoprenaline-induced relaxation showed reduced efficacy in OG, AG and OAG, when compared to CG. In the elucidation of the mechanism of contractile hyperreactivity to CCh, the probable participation of the superoxide anion and the cyclooxygenase products in asthma was characterized, the first being also a target of the OAH500G mechanism. In contrast, the participation of hydrogen peroxide, the nitric oxide pathway and 5-lipoxygenase products do not seem to be involved in the mechanisms of disease or hibiscus. However, a positive modulation of the Rho kinase pathway in GOA was evidenced, which was prevented by treatment of hibiscus. In view of these results, it is concluded that the obesity-exacerbated asthma model was implanted, which is resistant to treatment with dexamethasone, probably due to increased RhoA/ROCK activity. This effect is prevented by the treatment with hibiscus, becoming a promising drug for the treatment of this combined conditions.
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spelling Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de açãoHibiscus sabdariffaAsma exacerbada - ObesidadeVias aéreasReatividade contrátilExacerbated asthma - ObesityAirwayContractile reactivityCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAObesity and asthma combined result in an asthma phenotype with more severe symptoms and reduced response to corticosteroid treatment; however, the exact mechanism responsible for these changes remains unclear. In this context, a promising drug is Hibiscus sabdariffa L., popularly known as “hibiscus”, which has already shown anti-obesity activity and spasmolytic action in guinea pig trachea. Thus, the aim of this work was to standardize and implement a animal model of obesity-exacerbated asthma employing a high glycemic index diet (HGLI) and ovalbumin (OVA), characterizing in vivo and in vitro, morphologically, and functionally, the alterations induced by the combined diseases, evaluating also whether treatment with hibiscus would prevent the changes induced by them, characterizing its mechanism of action. Wistar rats (n = 5-6) were divided into control (CG), obese (OG), asthmatic (AG), obese asthmatic (OAG), obese asthmatic dexamethasone (OADEXAG), obese asthmatic hibiscus 250 mg/kg (OAH250G), obese asthmatic hibiscus 500 mg/kg (OAH500G) and obese asthmatic hibiscus 1000 mg/kg (OAH1000G). The experimental protocols were approved by CEUA/UFPB (5975030920). It was observed that obesity-related parameters, such as body weight, waist circumference, body mass index (BMI), and adiposity index were increased in OG and OAG. Treatment with dexamethasone caused weight loss compared to OAG, however, it did not reverse the increase in the other observed parameters. Hibiscus at doses of 500 and 1000 mg/kg prevented the increase in weight, BMI, abdominal circumference and adiposity. Histologically, an increase in the diameter of the adipose tissue in the animals fed with HGLI (OG and OAG) has been observed with prevention of these in OADEXAG and OAH500G. To characterize the implantation of asthma, lung function was measured using the spirometry technique (days 1, 12 and 21 of asthma induction) and no change in respiratory rate was observed, although a reduction in tidal volume and volume-minute on the 21st in AG and OAG has been reached, and this change was not reversed in OADEXAG and OAH500G. Lung histology demonstrated exacerbation of peribronchovascular inflammation in OAG compared to isolated diseases, as well as smooth muscle hypertrophy and extracellular matrix remodeling compared to CG. Functionally, the trachea was used to assess contractile and relaxing reactivity and elucidate the mechanism of action. Animals that were previously sensitized with OVA showed a contractile response to the allergen (AG and OAG), which was even greater in OAG and without reversion in OADEXAG or OAH500G. The electromechanical or histamine-induced contraction do not seemed to be involved in the diseases, with the exception of AG, which showed an increase in contractile efficacy with no change in potency against histamine. Otherwise, in the cumulative concentration-response curve to carbachol (CCh) has been observed an increase in contractile efficacy in OG, AG and OAG, with OAG being even greater than AG and with no change in potency between groups. This increase was not altered in OAH250G, however OAH500G and OAH100G prevented it, without changing the potency. On the other hand, the relaxing reactivity to nifedipine and aminophylline were not altered between the groups. While isoprenaline-induced relaxation showed reduced efficacy in OG, AG and OAG, when compared to CG. In the elucidation of the mechanism of contractile hyperreactivity to CCh, the probable participation of the superoxide anion and the cyclooxygenase products in asthma was characterized, the first being also a target of the OAH500G mechanism. In contrast, the participation of hydrogen peroxide, the nitric oxide pathway and 5-lipoxygenase products do not seem to be involved in the mechanisms of disease or hibiscus. However, a positive modulation of the Rho kinase pathway in GOA was evidenced, which was prevented by treatment of hibiscus. In view of these results, it is concluded that the obesity-exacerbated asthma model was implanted, which is resistant to treatment with dexamethasone, probably due to increased RhoA/ROCK activity. This effect is prevented by the treatment with hibiscus, becoming a promising drug for the treatment of this combined conditions.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqObesidade e asma quando associadas resultam em um fenótipo de asma com sintomas mais graves e redução da resposta ao tratamento com corticosteroides; entretanto, o exato mecanismo responsável por estas alterações permanece incerto. Nesse contexto, uma droga promissora é o Hibiscus sabdariffa L, popularmente conhecida como “hibisco”, que já demonstrou atividade antiobesidade e ação espasmolítica em traqueia de cobaia. Desta forma, o objetivo deste trabalho foi padronizar e implantar um modelo animal de asma exacerbada pela obesidade utilizando uma dieta de alto índice glicêmico (DAIG) e ovalbumina (OVA), caracterizando in vivo e in vitro, morfológica e funcionalmente, as alterações induzidas pela doença, avaliando também se o tratamento com o hibisco preveniria as alterações induzidas por esta, caracterizando o seu mecanismo de ação. Ratos Wistar (n = 5-6) foram divididos em grupos controle (GC), obeso (GO), asmático (GA), obeso asmático (GOA), obeso asmático dexametasona (GOADEXA), obeso asmático hibisco 250 mg/kg (GOAH250), obeso asmático hibisco 500 mg/kg (GOAH500) e obeso asmático hibisco 1000 mg/kg (GOAH1000). Os protocolos experimentais foram aprovados pela CEUA/UFPB (5975030920). Observou-se que parâmetros relacionados à obesidade, como peso corporal, circunferência abdominal, índice de massa corpórea (IMC) e índice de adiposidade foram aumentados nos GO e GOA. O tratamento com dexametasona ocasionou perda de peso comparado ao GOA, entretanto não reverteu o aumento dos demais parâmetros observados. Hibisco, nas doses de 500 e 1000 mg/kg, preveniu o aumento de peso, de IMC, da circunferência abdominal e da adiposidade. A indução da obesidade também foi comprovada histologicamente, com aumento do diâmetro do tecido adiposo nos animais que consumiram a DAIG (GO e GOA), havendo prevenção destas no GOADEXA e no GOAH500. Para caracterizar a implantação da asma, a função pulmonar foi avaliada através da técnica de espirometria (dias 1, 12 e 21 de indução da asma) e observou-se que não houve alteração da frequência respiratória, entretanto, ocorreu redução do volume corrente e volume-minuto no dia 21 nos GA e GOA e esta alteração não foi revertida no GOADEXA e no GOAH500. A histologia do pulmão demonstrou exacerbação da inflamação peribroncovascular no GOA em relação às doenças isoladamente, bem como hipertrofia do músculo liso e remodelamento da matriz extracelular, em comparação ao GC. Funcionalmente, a traqueia foi utilizada para avaliar a reatividade contrátil, relaxante e elucidar o mecanismo de ação. Os animais que foram previamente sensibilizados com OVA apresentaram resposta contrátil ao alérgeno (GA e GOA), sendo esta ainda maior no GOA e sem reversão nos GOADEXA ou no GOAH500. As vias eletromecânica ou induzida por histamina parecem não estar alteradas nas doenças, com exceção do GA que apresentou aumento da eficácia contrátil sem alteração da potência frente à histamina. Diferentemente, a adição de concentrações cumulativas de carbacol (CCh) induziu aumento da eficácia contrátil em GO, GA e GOA, sendo GOA ainda maior que GA e sem alteração da potência entre os grupos. Este aumento não foi alterado no GOAH250, porém GOAH500 e GOAH100 preveniram, sem alterar a potência. Já a reatividade relaxante ao nifedipino e à aminofilina não foram alteradas entre os grupos. Enquanto o relaxamento induzido por isoprenalina apresentou redução da eficácia nos GO, GA e GOA, quando comparado ao GC. Na elucidação do mecanismo de hiper-reatividade contrátil ao CCh, caracterizou-se a provável participação do ânion superóxido e dos produtos da cicloxigenase na asma, sendo o primeiro também alvo do mecanismo do hibisco. Diferentemente, a participação do péroxido de hidrogênio, da via do óxido nítrico e dos produtos da 5-lipoxigenase parecem não estar envolvidos nos mecanismos das doenças ou do hibisco. Entretanto, foi evidenciado uma modulação positiva da via Rho cinase no GOA, sendo este prevenido pelo tratamento com o hibisco. Diante destes resultados, conclui-se que um modelo inédito de asma exacerbada pela obesidade foi implantado, sendo este resistente ao tratamento com dexametasona, provavelmente ocorrendo por aumento da atividade de RhoA/ROCK. Este efeito é prevenido pelo tratamento com o hibisco, se tornando uma droga promissora para o tratamento desta condição.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBCavalcante, Fabiana de Andradehttp://lattes.cnpq.br/2233846820438278Vasconcelos, Luiz Henrique Césarhttp://lattes.cnpq.br/6948017014954499Ferreira, Sarah Rebeca Dantas2023-01-31T20:48:28Z2022-11-212023-01-31T20:48:28Z2022-08-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/26124porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2023-05-22T16:30:54Zoai:repositorio.ufpb.br:123456789/26124Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2023-05-22T16:30:54Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
title Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
spellingShingle Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
Ferreira, Sarah Rebeca Dantas
Hibiscus sabdariffa
Asma exacerbada - Obesidade
Vias aéreas
Reatividade contrátil
Exacerbated asthma - Obesity
Airway
Contractile reactivity
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
title_full Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
title_fullStr Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
title_full_unstemmed Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
title_sort Hibiscus sabdariffa L. previne alterações na composição corporal e na função e reatividade das vias aéreas de ratos submetidos a um modelo de asma exacerbada pela obesidade: determinação do mecanismo de ação
author Ferreira, Sarah Rebeca Dantas
author_facet Ferreira, Sarah Rebeca Dantas
author_role author
dc.contributor.none.fl_str_mv Cavalcante, Fabiana de Andrade
http://lattes.cnpq.br/2233846820438278
Vasconcelos, Luiz Henrique César
http://lattes.cnpq.br/6948017014954499
dc.contributor.author.fl_str_mv Ferreira, Sarah Rebeca Dantas
dc.subject.por.fl_str_mv Hibiscus sabdariffa
Asma exacerbada - Obesidade
Vias aéreas
Reatividade contrátil
Exacerbated asthma - Obesity
Airway
Contractile reactivity
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Hibiscus sabdariffa
Asma exacerbada - Obesidade
Vias aéreas
Reatividade contrátil
Exacerbated asthma - Obesity
Airway
Contractile reactivity
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Obesity and asthma combined result in an asthma phenotype with more severe symptoms and reduced response to corticosteroid treatment; however, the exact mechanism responsible for these changes remains unclear. In this context, a promising drug is Hibiscus sabdariffa L., popularly known as “hibiscus”, which has already shown anti-obesity activity and spasmolytic action in guinea pig trachea. Thus, the aim of this work was to standardize and implement a animal model of obesity-exacerbated asthma employing a high glycemic index diet (HGLI) and ovalbumin (OVA), characterizing in vivo and in vitro, morphologically, and functionally, the alterations induced by the combined diseases, evaluating also whether treatment with hibiscus would prevent the changes induced by them, characterizing its mechanism of action. Wistar rats (n = 5-6) were divided into control (CG), obese (OG), asthmatic (AG), obese asthmatic (OAG), obese asthmatic dexamethasone (OADEXAG), obese asthmatic hibiscus 250 mg/kg (OAH250G), obese asthmatic hibiscus 500 mg/kg (OAH500G) and obese asthmatic hibiscus 1000 mg/kg (OAH1000G). The experimental protocols were approved by CEUA/UFPB (5975030920). It was observed that obesity-related parameters, such as body weight, waist circumference, body mass index (BMI), and adiposity index were increased in OG and OAG. Treatment with dexamethasone caused weight loss compared to OAG, however, it did not reverse the increase in the other observed parameters. Hibiscus at doses of 500 and 1000 mg/kg prevented the increase in weight, BMI, abdominal circumference and adiposity. Histologically, an increase in the diameter of the adipose tissue in the animals fed with HGLI (OG and OAG) has been observed with prevention of these in OADEXAG and OAH500G. To characterize the implantation of asthma, lung function was measured using the spirometry technique (days 1, 12 and 21 of asthma induction) and no change in respiratory rate was observed, although a reduction in tidal volume and volume-minute on the 21st in AG and OAG has been reached, and this change was not reversed in OADEXAG and OAH500G. Lung histology demonstrated exacerbation of peribronchovascular inflammation in OAG compared to isolated diseases, as well as smooth muscle hypertrophy and extracellular matrix remodeling compared to CG. Functionally, the trachea was used to assess contractile and relaxing reactivity and elucidate the mechanism of action. Animals that were previously sensitized with OVA showed a contractile response to the allergen (AG and OAG), which was even greater in OAG and without reversion in OADEXAG or OAH500G. The electromechanical or histamine-induced contraction do not seemed to be involved in the diseases, with the exception of AG, which showed an increase in contractile efficacy with no change in potency against histamine. Otherwise, in the cumulative concentration-response curve to carbachol (CCh) has been observed an increase in contractile efficacy in OG, AG and OAG, with OAG being even greater than AG and with no change in potency between groups. This increase was not altered in OAH250G, however OAH500G and OAH100G prevented it, without changing the potency. On the other hand, the relaxing reactivity to nifedipine and aminophylline were not altered between the groups. While isoprenaline-induced relaxation showed reduced efficacy in OG, AG and OAG, when compared to CG. In the elucidation of the mechanism of contractile hyperreactivity to CCh, the probable participation of the superoxide anion and the cyclooxygenase products in asthma was characterized, the first being also a target of the OAH500G mechanism. In contrast, the participation of hydrogen peroxide, the nitric oxide pathway and 5-lipoxygenase products do not seem to be involved in the mechanisms of disease or hibiscus. However, a positive modulation of the Rho kinase pathway in GOA was evidenced, which was prevented by treatment of hibiscus. In view of these results, it is concluded that the obesity-exacerbated asthma model was implanted, which is resistant to treatment with dexamethasone, probably due to increased RhoA/ROCK activity. This effect is prevented by the treatment with hibiscus, becoming a promising drug for the treatment of this combined conditions.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-21
2022-08-12
2023-01-31T20:48:28Z
2023-01-31T20:48:28Z
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format doctoralThesis
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dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/26124
url https://repositorio.ufpb.br/jspui/handle/123456789/26124
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
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institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
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