Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Dias, Marília Leite
Orientador(a): Sousa, Francisca Cléa Florenço de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
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:
Dor
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/44078
Resumo: From the green fruit of Aniba riparia (Nees) Mez, some alcamides with interesting therapeutic potential, named Riparinas, are found. Through a process of chemical modification, a structural analogue of these substances, Riparina IV, was synthesized. Previous studies have shown that it has anxiolytic and antidepressant effects, as well as antinociceptive effect. The present work was developed with the approval of CEUA / UFC (nº 06/16), with the objective of evaluating the role of Rip.IV in the process of nociception and the pharmacological mechanisms related to its activity. Initially, male Swiss mice were used and experimental models of nociception were performed: acetic acid induced contortions, mechanical hypernociception induced by algic agents (PGE2 and epinephrine), nociception test induced by intraplantar injection of capsaicin, cinnamaldehyde, menthol, acidic saline, PMA And 8-Br-cAMP. In addition to the behavioral tests, the effect of Rip.IV on the Composite Action Potential (PAC) on the sciatic nerve of Wistar rats was analyzed. We performed a time curve with Rip.IV at a dose of 50mg / kg in the test of abdominal contortions induced by acetic acid, where it was observed that the effects of Rip.IV appeared after 30 minutes and persisted up to 240 minutes. Rip.IV (25 and 50 mg / kg, v.o.) was able to significantly reduce carragennan and PGE2-induced hypernociception, but did not present a statistically significant effect on the test performed with epinephrine. In the investigation of the antinociceptive mechanism, it was observed that Rip.IV demonstrated a PKA-related effect, as well as with ion channels related to this pathway. Rip IV blocked the positive amplitude of 1st and 2nd CAP in a concentration-dependent way, and these effects were reversible after washout. Both components reduced the conduction velocity of CAP similarly. The results demonstrate that Rip IV presents an antinociceptive effect related to inhibition of electric activity of peripheral nervous system.
id UFC-7_03d0337a28fb6591eb4b949b712df728
oai_identifier_str oai:repositorio.ufc.br:riufc/44078
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Dias, Marília LeiteSousa, Francisca Cléa Florenço de2019-07-25T10:24:40Z2019-07-25T10:24:40Z2017-06-28DIAS, M. L. Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos. 2017. 80 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, 2017.http://www.repositorio.ufc.br/handle/riufc/44078From the green fruit of Aniba riparia (Nees) Mez, some alcamides with interesting therapeutic potential, named Riparinas, are found. Through a process of chemical modification, a structural analogue of these substances, Riparina IV, was synthesized. Previous studies have shown that it has anxiolytic and antidepressant effects, as well as antinociceptive effect. The present work was developed with the approval of CEUA / UFC (nº 06/16), with the objective of evaluating the role of Rip.IV in the process of nociception and the pharmacological mechanisms related to its activity. Initially, male Swiss mice were used and experimental models of nociception were performed: acetic acid induced contortions, mechanical hypernociception induced by algic agents (PGE2 and epinephrine), nociception test induced by intraplantar injection of capsaicin, cinnamaldehyde, menthol, acidic saline, PMA And 8-Br-cAMP. In addition to the behavioral tests, the effect of Rip.IV on the Composite Action Potential (PAC) on the sciatic nerve of Wistar rats was analyzed. We performed a time curve with Rip.IV at a dose of 50mg / kg in the test of abdominal contortions induced by acetic acid, where it was observed that the effects of Rip.IV appeared after 30 minutes and persisted up to 240 minutes. Rip.IV (25 and 50 mg / kg, v.o.) was able to significantly reduce carragennan and PGE2-induced hypernociception, but did not present a statistically significant effect on the test performed with epinephrine. In the investigation of the antinociceptive mechanism, it was observed that Rip.IV demonstrated a PKA-related effect, as well as with ion channels related to this pathway. Rip IV blocked the positive amplitude of 1st and 2nd CAP in a concentration-dependent way, and these effects were reversible after washout. Both components reduced the conduction velocity of CAP similarly. The results demonstrate that Rip IV presents an antinociceptive effect related to inhibition of electric activity of peripheral nervous system.Do fruto verde da espécie Aniba riparia (Nees) Mez, são encontradas algumas alcamidas, denominadas Riparinas, que possuem um interessante potencial terapêutico. Através de um processo de modificação química, foi sintetizado um análogo estrutural dessas substâncias, a Riparina IV. Estudos anteriores mostraram que a mesma apresentou efeitos ansiolítico e antidepressivo, bem como efeito antinociceptivo. O presente trabalho foi desenvolvido com a aprovação pela CEUA/UFC (nº 06/16), com o objetivo de avaliar o papel da Rip.IV no processo de nocicepção e os mecanismos farmacológicos relacionados à sua atividade. Inicialmente, foram utilizados camundongos Swiss machos e realizados modelos experimentais de nocicepção: contorções induzidas pelo ácido acético, hipernocicepção mecânica induzida por agentes algésicos (PGE2 e epinefrina), teste de nocicepção induzida pela injeção intraplantar de capsaicina, cinamaldeído, mentol, salina ácida, PMA e 8-Br-AMPc. Além dos testes comportamentais, foi realizada análise do efeito da Rip.IV sobre o Potencial de Ação Composto (PAC) no nervo ciático de ratos Wistar. No teste das contorções abdominais induzidas por ácido acético foi realizada curva de tempo com a Rip.IV na dose de 50mg/kg, onde observou-se que os efeitos da Rip.IV apareceram após 30 minutos e persistiram até 240 minutos. A Rip.IV (25 e 50 mg/kg, v.o.) foi capaz de reduzir de forma significativa hipernocicepção induzida por carragenina e PGE2, porém não apresentou efeito estatisticamente significativo no teste realizado com epinefrina. Na investigação do mecanismo antinociceptivo, observou-se que a Rip.IV demonstrou um efeito relacionado com a PKA, bem como com canais iônicos relacionados a essa via. Em relação à ação de Rip IV sobre os parâmetros eletrofisiológicos nos axônios do nervo ciático, observou-se um bloqueio da amplitude positiva da amplitude de primeira e segunda componentes do potencial de ação composto (CAP) de forma concentração dependente, sendo os efeitos revertidos após a lavagem. A velocidade de ambas as componentes também foi reduzida de forma semelhante. Os resultados demonstram que a Rip IV apresenta efeito antinociceptivo relacionado com uma inibição da atividade elétrica do sistema nervoso periférico.NociceptividadeDorCarrageninaEfeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidosAntinociceptive activity of riparin IV in animal models: mechanisms involvedinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/44078/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINAL2017_tese_mldias.pdf2017_tese_mldias.pdfapplication/pdf1112845http://repositorio.ufc.br/bitstream/riufc/44078/3/2017_tese_mldias.pdff21adeb2840c27034a280bd4c9d7075eMD53riufc/440782019-10-22 15:39:08.466oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-22T18:39:08Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
dc.title.en.pt_BR.fl_str_mv Antinociceptive activity of riparin IV in animal models: mechanisms involved
title Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
spellingShingle Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
Dias, Marília Leite
Nociceptividade
Dor
Carragenina
title_short Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
title_full Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
title_fullStr Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
title_full_unstemmed Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
title_sort Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos
author Dias, Marília Leite
author_facet Dias, Marília Leite
author_role author
dc.contributor.author.fl_str_mv Dias, Marília Leite
dc.contributor.advisor1.fl_str_mv Sousa, Francisca Cléa Florenço de
contributor_str_mv Sousa, Francisca Cléa Florenço de
dc.subject.por.fl_str_mv Nociceptividade
Dor
Carragenina
topic Nociceptividade
Dor
Carragenina
description From the green fruit of Aniba riparia (Nees) Mez, some alcamides with interesting therapeutic potential, named Riparinas, are found. Through a process of chemical modification, a structural analogue of these substances, Riparina IV, was synthesized. Previous studies have shown that it has anxiolytic and antidepressant effects, as well as antinociceptive effect. The present work was developed with the approval of CEUA / UFC (nº 06/16), with the objective of evaluating the role of Rip.IV in the process of nociception and the pharmacological mechanisms related to its activity. Initially, male Swiss mice were used and experimental models of nociception were performed: acetic acid induced contortions, mechanical hypernociception induced by algic agents (PGE2 and epinephrine), nociception test induced by intraplantar injection of capsaicin, cinnamaldehyde, menthol, acidic saline, PMA And 8-Br-cAMP. In addition to the behavioral tests, the effect of Rip.IV on the Composite Action Potential (PAC) on the sciatic nerve of Wistar rats was analyzed. We performed a time curve with Rip.IV at a dose of 50mg / kg in the test of abdominal contortions induced by acetic acid, where it was observed that the effects of Rip.IV appeared after 30 minutes and persisted up to 240 minutes. Rip.IV (25 and 50 mg / kg, v.o.) was able to significantly reduce carragennan and PGE2-induced hypernociception, but did not present a statistically significant effect on the test performed with epinephrine. In the investigation of the antinociceptive mechanism, it was observed that Rip.IV demonstrated a PKA-related effect, as well as with ion channels related to this pathway. Rip IV blocked the positive amplitude of 1st and 2nd CAP in a concentration-dependent way, and these effects were reversible after washout. Both components reduced the conduction velocity of CAP similarly. The results demonstrate that Rip IV presents an antinociceptive effect related to inhibition of electric activity of peripheral nervous system.
publishDate 2017
dc.date.issued.fl_str_mv 2017-06-28
dc.date.accessioned.fl_str_mv 2019-07-25T10:24:40Z
dc.date.available.fl_str_mv 2019-07-25T10:24:40Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv DIAS, M. L. Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos. 2017. 80 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, 2017.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/44078
identifier_str_mv DIAS, M. L. Efeito antinociceptivo da riparina IV em modelos animais: mecanismos de ação envolvidos. 2017. 80 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, 2017.
url http://www.repositorio.ufc.br/handle/riufc/44078
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/44078/2/license.txt
http://repositorio.ufc.br/bitstream/riufc/44078/3/2017_tese_mldias.pdf
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
f21adeb2840c27034a280bd4c9d7075e
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1847792987011022848