Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético

Detalhes bibliográficos
Ano de defesa: 2013
Autor(a) principal: Lima Júnior, Francisco José Batista de
Orientador(a): Magalhães, Pedro Jorge Caldas
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
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/15656
Resumo: It was previously shown that the essential oil of Ocimum micranthum (EOOM), and its major constituent, methyl cinnamate (MC), have myorelaxant action on tracheal smooth muscle, airway anti-inflammatory and anti-nociceptive on rodents. The present work aimed to evaluate the antispasmodic and anti-inflammatory potential of MC on gastrointestinal tissues from rats subjected to acetic acid-induced colitis model. EOOM inhibited carbamylcholine- (CCh; 1 M) and KCl-induced (60 mM) contractions in stomach fundus strips with IC50 of 91.9 g/mL and 46.8 g/mL, respectively. It significantly reduced the basal tonus as well as the spontaneous contractions in duodenum. The isomers (Z)- or (E)-MC also inhibited CCh and KCl contractions in fundus, antrum, duodenum and colon strips, without differences between the effects caused by the isomers in each segment. MC significantly inhibited CCh in lower concentration in comparison with KCl, but with decreased potency if compared to atropine. (E)-MC inhibited intracellular calcium stores-dependent contractions, and its effect seems not to involve the activity of the nitric oxide synthase or the opening of potassium channels. Analyzed by confocal microscopy, freshly dissociated colon cells showed reduced basal cytosolic calcium levels (60%) after (E)-MC (600 M) exposure. In vivo, a first dose of (E)-MC (50 mg/kg) did not affect gastric contractions, but following a second dosage (50 mg/kg) administered a half an hour later, it reduced gastric contractions for 10 minutes. Colitis was induced by rectal instillation of acetic acid 5%. Sham group received only saline in instillation, while treated groups, beyond acid instillation, received (E)-CM 50 mg/kg/day p.o. or prednisolone 1 mg/kg/day p.o. during three days. Acetic acid instillation induced colitis that was macroscopically confirmed, leukocytosis, increased interleucin-1β and functional response loss due to voltage operated calcium channel disorder. These parameters were recovered by (E)-MC or prednisolone. Therefore, EOOM and CM have in vitro antispasmodic effect on rat gastrointestinal tract. The effect of CM involves reduction of the intracellular levels of calcium being independent of the nitric oxide synthase and potassium channels. CM has anti-inflammatory action comparable to prednisolone in magnitude.
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spelling Lima Júnior, Francisco José Batista deMagalhães, Pedro Jorge Caldas2016-03-22T13:28:09Z2016-03-22T13:28:09Z2013LIMA JÚNIOR, F. J. B. de. Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético. 2013. 99 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013.http://www.repositorio.ufc.br/handle/riufc/15656It was previously shown that the essential oil of Ocimum micranthum (EOOM), and its major constituent, methyl cinnamate (MC), have myorelaxant action on tracheal smooth muscle, airway anti-inflammatory and anti-nociceptive on rodents. The present work aimed to evaluate the antispasmodic and anti-inflammatory potential of MC on gastrointestinal tissues from rats subjected to acetic acid-induced colitis model. EOOM inhibited carbamylcholine- (CCh; 1 M) and KCl-induced (60 mM) contractions in stomach fundus strips with IC50 of 91.9 g/mL and 46.8 g/mL, respectively. It significantly reduced the basal tonus as well as the spontaneous contractions in duodenum. The isomers (Z)- or (E)-MC also inhibited CCh and KCl contractions in fundus, antrum, duodenum and colon strips, without differences between the effects caused by the isomers in each segment. MC significantly inhibited CCh in lower concentration in comparison with KCl, but with decreased potency if compared to atropine. (E)-MC inhibited intracellular calcium stores-dependent contractions, and its effect seems not to involve the activity of the nitric oxide synthase or the opening of potassium channels. Analyzed by confocal microscopy, freshly dissociated colon cells showed reduced basal cytosolic calcium levels (60%) after (E)-MC (600 M) exposure. In vivo, a first dose of (E)-MC (50 mg/kg) did not affect gastric contractions, but following a second dosage (50 mg/kg) administered a half an hour later, it reduced gastric contractions for 10 minutes. Colitis was induced by rectal instillation of acetic acid 5%. Sham group received only saline in instillation, while treated groups, beyond acid instillation, received (E)-CM 50 mg/kg/day p.o. or prednisolone 1 mg/kg/day p.o. during three days. Acetic acid instillation induced colitis that was macroscopically confirmed, leukocytosis, increased interleucin-1β and functional response loss due to voltage operated calcium channel disorder. These parameters were recovered by (E)-MC or prednisolone. Therefore, EOOM and CM have in vitro antispasmodic effect on rat gastrointestinal tract. The effect of CM involves reduction of the intracellular levels of calcium being independent of the nitric oxide synthase and potassium channels. CM has anti-inflammatory action comparable to prednisolone in magnitude.Previamente demonstrou-se que o óleo essencial de Ocimum micranthum (OEOM) e seu constituinte majoritário, cinamato de metila (CM), têm ações miorrelaxante e antinflamatória em tecidos traqueais de ratos, e efeito antinociceptivo em camundongos. O objetivo deste estudo foi avaliar o potencial antiespasmódico e anti-inflamatório do CM no trato gastrintestinal de ratos submetidos a modelo de colite induzida por ácido acético. OEOM inibiu contrações induzidas por carbamilcolina (CCh; 1 M) e KCl (60 mM) em tiras de fundo de estômago com CI50 de 91,9 g/mL e 46,8 g/mL, respectivamente, e reduziu significativamente o tônus basal e amplitudes de contrações espontâneas de duodeno. CM, em conformações isoméricas (Z)- ou (E)-, também inibiu essas respostas induzidas por CCh e KCl em fundo, antro, duodeno e cólon, sem diferenças nos efeitos dos isômeros em cada segmento. CM começa a inibir as contrações induzidas por CCh em concentração mais baixa que KCl, contudo com potência menor se comparado aos efeitos da atropina. (E)-CM inibe contrações dependentes dos estoques intracelulares de cálcio, e seu efeito inibitório parece não depender da ação da óxido nítrico sintase ou da abertura de canais de potássio. Analisadas em microscópio confocal, células de cólon dissociadas a fresco tiveram nível citossólico de cálcio reduzido para 60% do basal após exposição a (E)-CM (600M). Avaliando a pressão intragástrica in vivo, uma dose de (E)-CM 50 mg/kg não afeta amplitude das contrações gástricas, mas se repetida após 30 minutos, as diminui por até 10 minutos. A indução de colite foi através de instilação de ácido acético a 5% via retal. O grupo sham recebeu instilação apenas de salina, e os grupos tratados, além da instilação de ácido receberam (E)-CM 50 mg/kg/dia ou prednisolona 1 mg/kg/dia durante três dias. A instilação com ácido acético induziu colite confirmada por alteração macroscópica, leucocitose, aumento de interleucina-1 tecidual e déficit funcional de resposta dependente de canais para cálcio operados por voltagem. Esses parâmetros foram revertidos pelos tratamentos com (E)-CM e prednisolona. Portanto, OEOM e CM apresentam ação antiespasmódica em trato gastrintestinal de ratos in vitro. O efeito do CM passa pela redução dos níveis intracelulares basais de cálcio e independe da participação da enzima óxido nítrico sintase e de canais de potássio. CM possui ação anti-inflamatória de magnitude comparável à prednisolona.Trato GastrointestinalColiteAção antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acéticoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2013_dis_fjblimajunior.pdf2013_dis_fjblimajunior.pdfapplication/pdf1622438http://repositorio.ufc.br/bitstream/riufc/15656/1/2013_dis_fjblimajunior.pdfe5689fb1a406f1c272a9eb1e4d38c2b6MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81786http://repositorio.ufc.br/bitstream/riufc/15656/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52riufc/156562021-07-09 17:34:31.84oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-07-09T20:34:31Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
title Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
spellingShingle Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
Lima Júnior, Francisco José Batista de
Trato Gastrointestinal
Colite
title_short Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
title_full Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
title_fullStr Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
title_full_unstemmed Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
title_sort Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético
author Lima Júnior, Francisco José Batista de
author_facet Lima Júnior, Francisco José Batista de
author_role author
dc.contributor.author.fl_str_mv Lima Júnior, Francisco José Batista de
dc.contributor.advisor1.fl_str_mv Magalhães, Pedro Jorge Caldas
contributor_str_mv Magalhães, Pedro Jorge Caldas
dc.subject.por.fl_str_mv Trato Gastrointestinal
Colite
topic Trato Gastrointestinal
Colite
description It was previously shown that the essential oil of Ocimum micranthum (EOOM), and its major constituent, methyl cinnamate (MC), have myorelaxant action on tracheal smooth muscle, airway anti-inflammatory and anti-nociceptive on rodents. The present work aimed to evaluate the antispasmodic and anti-inflammatory potential of MC on gastrointestinal tissues from rats subjected to acetic acid-induced colitis model. EOOM inhibited carbamylcholine- (CCh; 1 M) and KCl-induced (60 mM) contractions in stomach fundus strips with IC50 of 91.9 g/mL and 46.8 g/mL, respectively. It significantly reduced the basal tonus as well as the spontaneous contractions in duodenum. The isomers (Z)- or (E)-MC also inhibited CCh and KCl contractions in fundus, antrum, duodenum and colon strips, without differences between the effects caused by the isomers in each segment. MC significantly inhibited CCh in lower concentration in comparison with KCl, but with decreased potency if compared to atropine. (E)-MC inhibited intracellular calcium stores-dependent contractions, and its effect seems not to involve the activity of the nitric oxide synthase or the opening of potassium channels. Analyzed by confocal microscopy, freshly dissociated colon cells showed reduced basal cytosolic calcium levels (60%) after (E)-MC (600 M) exposure. In vivo, a first dose of (E)-MC (50 mg/kg) did not affect gastric contractions, but following a second dosage (50 mg/kg) administered a half an hour later, it reduced gastric contractions for 10 minutes. Colitis was induced by rectal instillation of acetic acid 5%. Sham group received only saline in instillation, while treated groups, beyond acid instillation, received (E)-CM 50 mg/kg/day p.o. or prednisolone 1 mg/kg/day p.o. during three days. Acetic acid instillation induced colitis that was macroscopically confirmed, leukocytosis, increased interleucin-1β and functional response loss due to voltage operated calcium channel disorder. These parameters were recovered by (E)-MC or prednisolone. Therefore, EOOM and CM have in vitro antispasmodic effect on rat gastrointestinal tract. The effect of CM involves reduction of the intracellular levels of calcium being independent of the nitric oxide synthase and potassium channels. CM has anti-inflammatory action comparable to prednisolone in magnitude.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-03-22T13:28:09Z
dc.date.available.fl_str_mv 2016-03-22T13:28:09Z
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dc.identifier.citation.fl_str_mv LIMA JÚNIOR, F. J. B. de. Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético. 2013. 99 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/15656
identifier_str_mv LIMA JÚNIOR, F. J. B. de. Ação antiespasmódica gastrintestinal e potencial efeito anti-inflamatório do cinamato de metila em ratos sujeitos a modelo de colite por ácido acético. 2013. 99 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013.
url http://www.repositorio.ufc.br/handle/riufc/15656
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