Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico

Detalhes bibliográficos
Autor(a) principal: Belém, Mônica de Oliveira
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/62463
Resumo: Gastrintestinal (GI) tract is closely related to central nervous system, with repercussions resulting from anxiety disorder, depression and stress. As a new therapeutic approach possibility to these disorders, Ayahuasca appears, but still without evaluating its reflex in GI tract. The objective was to evaluate chronic physical stress (CPS) repercussions on morphology, motility, permeability and contractility of Swiss mice gastrointestinal tract, as well as biological effect of β-carbolines derived from Ayahuasca for treatment of these chanEs. CPS induction occurred over eleven consecutive days by restraining movement (3h/day), followed by solid fasting (12h/dark cycle). The animals were treated (IP) with βcarbolines harmine (HM, 15mg/kg), harmaline (HL, 20mg/kg) or tetrahydroharmine (THH, 1, 10 or 30mg/kg) from fifth to 11th day or prepared from three active ingredients, the pharmahuasca (PH), on fifth and eighth induction day. Survival, body mass, feed and water consumption, body composition, gastric emptying (E) of liquid and solid, in vitro contractility, transepithelial resistance (TERE) and intestinal permeability, and transmural GI tract morphometry were evaluated. The stress per si caused reduced survival, weight loss, inversion of food consumption pattern, intense free fat mass loss and had a dual impact on E, with acceleration in liquids and delay in solid food, associated with gastric antrum lower contractile responsiveness, and duodenum hypercontractility. Associated with this, stress reduces TERE, without altering intestinal permeability. Added to this, thinning of structures lumen closer in small intestine, while in colon, transmural thickening or flattening was observed, region evaluated depending. It was also noted that environment has an important influence on chanEs appearance when animals submitted or not to stress were kept in a shared environment. Finally, vagus-vagal innervation integrity was also found to play a fundamental role in appearance of alterations resulting from CPS. When treated with β-carbolines derived from Ayahuasca, it was noted that, despite sharing the same pharmacological action mechanism, each treatment and whether administered alone or in a pharmahuasca preparation, respond differently to chanEs in the GI tract of animals under CPS. FH per si apparently does not alter E basal functioning, whereas in a stressful situation, it causes EG of liquids and solids delays, associated with lower gastric antrum and duodenal responsiveness to pharmacomechanical and pharmacochemical stimuli. The repercussion in E to THH was dose dependent, since in a low dose (1 mg/kg) it regulates E of liquid rate, whereas in an intermediate dose (10 mg/kg) it causes acceleration and in a high dose (30 mg/kg) delay this phenomenon. On the other hand, treatment with HM or HL was able to abolish E chanEs, caused by CPS, inducing less gastric fundus and antrum contractile responsiveness. Thus, it is concluded that β-carbolines derived from Ayahuasca can be considered in treatment of repercussion of chronic physical stress on the gastrointestinal tract.
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spelling Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônicoEsvaziamento GástricoEstresseMotilidade GastrintestinalBanisteriopsisCarbolinasGastrintestinal (GI) tract is closely related to central nervous system, with repercussions resulting from anxiety disorder, depression and stress. As a new therapeutic approach possibility to these disorders, Ayahuasca appears, but still without evaluating its reflex in GI tract. The objective was to evaluate chronic physical stress (CPS) repercussions on morphology, motility, permeability and contractility of Swiss mice gastrointestinal tract, as well as biological effect of β-carbolines derived from Ayahuasca for treatment of these chanEs. CPS induction occurred over eleven consecutive days by restraining movement (3h/day), followed by solid fasting (12h/dark cycle). The animals were treated (IP) with βcarbolines harmine (HM, 15mg/kg), harmaline (HL, 20mg/kg) or tetrahydroharmine (THH, 1, 10 or 30mg/kg) from fifth to 11th day or prepared from three active ingredients, the pharmahuasca (PH), on fifth and eighth induction day. Survival, body mass, feed and water consumption, body composition, gastric emptying (E) of liquid and solid, in vitro contractility, transepithelial resistance (TERE) and intestinal permeability, and transmural GI tract morphometry were evaluated. The stress per si caused reduced survival, weight loss, inversion of food consumption pattern, intense free fat mass loss and had a dual impact on E, with acceleration in liquids and delay in solid food, associated with gastric antrum lower contractile responsiveness, and duodenum hypercontractility. Associated with this, stress reduces TERE, without altering intestinal permeability. Added to this, thinning of structures lumen closer in small intestine, while in colon, transmural thickening or flattening was observed, region evaluated depending. It was also noted that environment has an important influence on chanEs appearance when animals submitted or not to stress were kept in a shared environment. Finally, vagus-vagal innervation integrity was also found to play a fundamental role in appearance of alterations resulting from CPS. When treated with β-carbolines derived from Ayahuasca, it was noted that, despite sharing the same pharmacological action mechanism, each treatment and whether administered alone or in a pharmahuasca preparation, respond differently to chanEs in the GI tract of animals under CPS. FH per si apparently does not alter E basal functioning, whereas in a stressful situation, it causes EG of liquids and solids delays, associated with lower gastric antrum and duodenal responsiveness to pharmacomechanical and pharmacochemical stimuli. The repercussion in E to THH was dose dependent, since in a low dose (1 mg/kg) it regulates E of liquid rate, whereas in an intermediate dose (10 mg/kg) it causes acceleration and in a high dose (30 mg/kg) delay this phenomenon. On the other hand, treatment with HM or HL was able to abolish E chanEs, caused by CPS, inducing less gastric fundus and antrum contractile responsiveness. Thus, it is concluded that β-carbolines derived from Ayahuasca can be considered in treatment of repercussion of chronic physical stress on the gastrointestinal tract.O trato gastrintestinal (TGI) guarda íntima relação com o sistema nervoso central, com repercussões decorrentes de transtorno de ansiedade, depressão e estresse. Como nova possibilidade de abordagem terapêutica a esses transtornos, surge a Ayahuasca, porém ainda sem avaliar seu reflexo no TGI. Objetivou-se avaliar as repercussões do estresse físico crônico (EFC) sobre a morfologia, motilidade, permeabilidade e contratilidade do trato gastrintestinal de camundongos Swiss, assim como o efeito biológico das β-carbolinas derivadas da Ayahuasca para o tratamento dessas alterações. A indução do EFC ocorreu ao longo de onze dias consecutivos por contenção de movimento (3h/dia), seguido de jejum sólido (12h/ciclo escuro). Os animais foram tratados (IP) com as β-carbolinas harmina (HM, 15mg/kg), harmalina (HL, 20mg/kg) ou tetrahidroharmina (THH, 1, 10 ou 30mg/kg) do quinto ao 11° dia ou o preparado dos três princípios ativos, a farmahuasca (FH), ao quinto e oitavo dia de indução. Avaliou-se a sobrevida, massa corporal, consumo de ração e água, composição corporal, esvaziamento gástrico (EG) de líquido e sólido, contratilidade in vitro, resistência transepitelial (RETE) e permeabilidade intestinal, e morfometrial transmural do TGI. O estresse per si causou redução da sobrevida, perda de peso, inversão do padrão de consumo alimentar, intensa perda de massa magra e repercutiu de forma dual sobre o EG, com aceleração em líquidos e retarde em alimento sólido, associado à menor responsividade contrátil do antro gástrico, e hipercontratilidade do duodeno. Associado a isso, o estresse reduz a RETE, sem alterar a permeabilidade intestinal. Soma-se a isso, o adelgaçamento de estruturas mais próximas ao lúmen do intestino delgado, ao passo que, no cólon observou-se espessamento ou achatamento transmural, a depender da região avaliada. Notou-se ainda, que o ambiente tem importante influência no aparecimento dessas alterações, quando animais submetidos ou não ao estresse eram mantidos em ambiente compartilhado. Por fim, constatou-se a integridade da inervação vago-vagal também desempenha papel fundamental no aparecimento das alterações decorrentes do EFC. Quando tratados com as β-carbolinas derivadas da Ayahuasca, notou-se que, apesar de compartilharem no mesmo mecanismo de ação farmacológica, cada tratamento e se administrados de forma isolada ou em preparado de farmahuasca, respondem de forma distinta às alterações do TGI de animais sob EFC. A FH per si aparentemente não altera o funcionamento basal do EG, ao passo que em situação de estresse, causa retarde do EG de líquidos e sólidos, associado à menor responsividade de fundo e antro gástrico e duodeno aos estímulos farmacomecênicos e farmacoquímicos. A repercussão no EG da THH mostrou-se dose dependente, uma vez que em baixa dose (1 mg/kg) regulariza a taxa de EG de líquido, ao passo que em dose intermediária (10 mg/kg) causa aceleração e em dose alta (30 mg/kg) o retarde desse fenômeno. Por outro lado, o tratamento com HM ou HL foi capaz de abolir as alterações do EG, causadas pelo EFC, induzindo a menor responsividade contrátil de fundo e antro gástricos. Assim, conclui-se que as β-carbolinas derivadas da Ayahuasca possam ser consideradas no tratamento da repercussão do estresse físico crônico sobre o trato gastrintestinal.Santos, Armênio Aguiar dosBelém, Mônica de Oliveira2021-11-25T13:15:05Z2021-11-25T13:15:05Z2021-07-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfBELÉM, Mônica de Oliveira. Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico. 2021. Tese ( Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62463. Acesso em: 25/11/2021.http://www.repositorio.ufc.br/handle/riufc/62463porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2023-10-23T14:33:42Zoai:repositorio.ufc.br:riufc/62463Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:52:17.884121Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
title Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
spellingShingle Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
Belém, Mônica de Oliveira
Esvaziamento Gástrico
Estresse
Motilidade Gastrintestinal
Banisteriopsis
Carbolinas
title_short Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
title_full Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
title_fullStr Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
title_full_unstemmed Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
title_sort Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico
author Belém, Mônica de Oliveira
author_facet Belém, Mônica de Oliveira
author_role author
dc.contributor.none.fl_str_mv Santos, Armênio Aguiar dos
dc.contributor.author.fl_str_mv Belém, Mônica de Oliveira
dc.subject.por.fl_str_mv Esvaziamento Gástrico
Estresse
Motilidade Gastrintestinal
Banisteriopsis
Carbolinas
topic Esvaziamento Gástrico
Estresse
Motilidade Gastrintestinal
Banisteriopsis
Carbolinas
description Gastrintestinal (GI) tract is closely related to central nervous system, with repercussions resulting from anxiety disorder, depression and stress. As a new therapeutic approach possibility to these disorders, Ayahuasca appears, but still without evaluating its reflex in GI tract. The objective was to evaluate chronic physical stress (CPS) repercussions on morphology, motility, permeability and contractility of Swiss mice gastrointestinal tract, as well as biological effect of β-carbolines derived from Ayahuasca for treatment of these chanEs. CPS induction occurred over eleven consecutive days by restraining movement (3h/day), followed by solid fasting (12h/dark cycle). The animals were treated (IP) with βcarbolines harmine (HM, 15mg/kg), harmaline (HL, 20mg/kg) or tetrahydroharmine (THH, 1, 10 or 30mg/kg) from fifth to 11th day or prepared from three active ingredients, the pharmahuasca (PH), on fifth and eighth induction day. Survival, body mass, feed and water consumption, body composition, gastric emptying (E) of liquid and solid, in vitro contractility, transepithelial resistance (TERE) and intestinal permeability, and transmural GI tract morphometry were evaluated. The stress per si caused reduced survival, weight loss, inversion of food consumption pattern, intense free fat mass loss and had a dual impact on E, with acceleration in liquids and delay in solid food, associated with gastric antrum lower contractile responsiveness, and duodenum hypercontractility. Associated with this, stress reduces TERE, without altering intestinal permeability. Added to this, thinning of structures lumen closer in small intestine, while in colon, transmural thickening or flattening was observed, region evaluated depending. It was also noted that environment has an important influence on chanEs appearance when animals submitted or not to stress were kept in a shared environment. Finally, vagus-vagal innervation integrity was also found to play a fundamental role in appearance of alterations resulting from CPS. When treated with β-carbolines derived from Ayahuasca, it was noted that, despite sharing the same pharmacological action mechanism, each treatment and whether administered alone or in a pharmahuasca preparation, respond differently to chanEs in the GI tract of animals under CPS. FH per si apparently does not alter E basal functioning, whereas in a stressful situation, it causes EG of liquids and solids delays, associated with lower gastric antrum and duodenal responsiveness to pharmacomechanical and pharmacochemical stimuli. The repercussion in E to THH was dose dependent, since in a low dose (1 mg/kg) it regulates E of liquid rate, whereas in an intermediate dose (10 mg/kg) it causes acceleration and in a high dose (30 mg/kg) delay this phenomenon. On the other hand, treatment with HM or HL was able to abolish E chanEs, caused by CPS, inducing less gastric fundus and antrum contractile responsiveness. Thus, it is concluded that β-carbolines derived from Ayahuasca can be considered in treatment of repercussion of chronic physical stress on the gastrointestinal tract.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-25T13:15:05Z
2021-11-25T13:15:05Z
2021-07-30
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dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
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dc.identifier.uri.fl_str_mv BELÉM, Mônica de Oliveira. Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico. 2021. Tese ( Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62463. Acesso em: 25/11/2021.
http://www.repositorio.ufc.br/handle/riufc/62463
identifier_str_mv BELÉM, Mônica de Oliveira. Efeitos das β-carbolinas derivadas da ayahuasca sobre as repercussões morfofuncionais do trato gastrintestinal de camundongos submetidos ao estresse físico crônico. 2021. Tese ( Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62463. Acesso em: 25/11/2021.
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