Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos
Ano de defesa: | 2019 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/21004 |
Resumo: | The inflammation is a multicelular and complex process that has an essential protective role in the body. However, it can become pathological when it acts with excessive intensity and prolong endurance. In addition, the available therapeutic options to counteract inflammation has some issues regarding efficacy and safety use. In this context, the development of novel molecules with improved pharmacological profile is necessary. The m-trifluoromethyl-dyphenil diselenide [(m-CF3-PhSe)2] is an organoselenium compound that has promising biological properties, including antinociceptive action in experimental models of nociception. Thus, the main purpose of this dissertation was to evaluate the (m-CF3-PhSe)2 anti-inflammatory action in models of acute and subchronic inflammation induced by complete Freund’s adjuvant (CFA) in Swiss adult mice. The Ethical Research Committee of Federal University of Santa Maria approved all experimental procedures carried out in the present study, which are register under the number 8081170317/2017. Initially, the physicochemical stability of (m-CF3- PhSe)2 in different storage conditions was evaluated. Our results demonstrated that independent of time and storage conditions tested (freezer [-20 ºC], refrigeration [4 ºC] or room temperature [25 ºC]) no alteration in compound content was detected, suggesting a high chemical stability of (m-CF3- PhSe)2. In the protocol 1, the acute inflammation was induced in mice by an intraplantar injection of CFA and 24 h later they received a single intragastric (i.g.) administration of (m-CF3-PhSe)2. A time- and dose-response curve was performed to assess the (m-CF3-PhSe)2 effect in the mechanical hypernociception, using the von Frey hair (VFH), paw edema and myeloperoxidase activity induced by CFA. The treatment with (m-CF3-PhSe)2 reduced the mechanical hypernociceptive behavior (10 and 1 mg/kg, i.g.) as well as mitigated the paw thickness and MPO activity (10 mg/kg, i.g.). Following, the protocol 2 evaluated the effectiveness of a repeated treatment schedule with (m-CF3-PhSe)2 against the inflammatory impairments induced by CFA in mice. The potential toxicity of such administration schedule was also assessed. Mice received an intraplantar injection of CFA and 14 days later they were treated with (m-CF3-PhSe)2 (1 mg/kg, i.g./once a day/10 days). The mechanical and thermal hypernociception were daily recorded using VFH test and hot-plate test (52 ºC), respectively. The results demonstrated that the repeated administration of (m-CF3-PhSe)2 reduced both mechanical and thermal hypernociception induced by CFA. In addition, the repeated treatment with (m-CF3-PhSe)2 restored the biochemical (edema and MPO activity of paw) and molecular (IL-1β, TNF-α e COX-2, assessed in cerebral contralateral cortex samples) impairments caused by CFA. Furthermore, the repeated (m-CF3-PhSe)2 administration triggered no alteration in locomotor and exploratory activity (number of crossing, distance and average speed), plasma biochemical parameters (hepatic, renal and cardiac function) as well as in the tissue oxidative status (liver and kidneys). Collectively, these data support the (m-CF3-PhSe)2 anti-inflammatory action, reinforcing the pharmacological potential of the compound. |
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2021-05-27T18:52:14Z2021-05-27T18:52:14Z2019-02-21http://repositorio.ufsm.br/handle/1/21004The inflammation is a multicelular and complex process that has an essential protective role in the body. However, it can become pathological when it acts with excessive intensity and prolong endurance. In addition, the available therapeutic options to counteract inflammation has some issues regarding efficacy and safety use. In this context, the development of novel molecules with improved pharmacological profile is necessary. The m-trifluoromethyl-dyphenil diselenide [(m-CF3-PhSe)2] is an organoselenium compound that has promising biological properties, including antinociceptive action in experimental models of nociception. Thus, the main purpose of this dissertation was to evaluate the (m-CF3-PhSe)2 anti-inflammatory action in models of acute and subchronic inflammation induced by complete Freund’s adjuvant (CFA) in Swiss adult mice. The Ethical Research Committee of Federal University of Santa Maria approved all experimental procedures carried out in the present study, which are register under the number 8081170317/2017. Initially, the physicochemical stability of (m-CF3- PhSe)2 in different storage conditions was evaluated. Our results demonstrated that independent of time and storage conditions tested (freezer [-20 ºC], refrigeration [4 ºC] or room temperature [25 ºC]) no alteration in compound content was detected, suggesting a high chemical stability of (m-CF3- PhSe)2. In the protocol 1, the acute inflammation was induced in mice by an intraplantar injection of CFA and 24 h later they received a single intragastric (i.g.) administration of (m-CF3-PhSe)2. A time- and dose-response curve was performed to assess the (m-CF3-PhSe)2 effect in the mechanical hypernociception, using the von Frey hair (VFH), paw edema and myeloperoxidase activity induced by CFA. The treatment with (m-CF3-PhSe)2 reduced the mechanical hypernociceptive behavior (10 and 1 mg/kg, i.g.) as well as mitigated the paw thickness and MPO activity (10 mg/kg, i.g.). Following, the protocol 2 evaluated the effectiveness of a repeated treatment schedule with (m-CF3-PhSe)2 against the inflammatory impairments induced by CFA in mice. The potential toxicity of such administration schedule was also assessed. Mice received an intraplantar injection of CFA and 14 days later they were treated with (m-CF3-PhSe)2 (1 mg/kg, i.g./once a day/10 days). The mechanical and thermal hypernociception were daily recorded using VFH test and hot-plate test (52 ºC), respectively. The results demonstrated that the repeated administration of (m-CF3-PhSe)2 reduced both mechanical and thermal hypernociception induced by CFA. In addition, the repeated treatment with (m-CF3-PhSe)2 restored the biochemical (edema and MPO activity of paw) and molecular (IL-1β, TNF-α e COX-2, assessed in cerebral contralateral cortex samples) impairments caused by CFA. Furthermore, the repeated (m-CF3-PhSe)2 administration triggered no alteration in locomotor and exploratory activity (number of crossing, distance and average speed), plasma biochemical parameters (hepatic, renal and cardiac function) as well as in the tissue oxidative status (liver and kidneys). Collectively, these data support the (m-CF3-PhSe)2 anti-inflammatory action, reinforcing the pharmacological potential of the compound.A inflamação é um processo multicelular e complexo que tem um papel protetor essencial no corpo. No entanto, pode tornar-se patológico quando age com intensidade excessiva e prolongada resistência. Além disso, as opções terapêuticas disponíveis para combater a inflamação apresentam algumas questões relacionadas à eficácia e à segurança. Neste contexto, o desenvolvimento de novas moléculas com perfil farmacológico melhorado é necessário. O disseleneto de m-trifluormetil difenila [(m-CF3-PhSe)2] é um composto orgânico de selênio que possui propriedades biológicas promissoras, incluindo ação antinociceptiva em modelos experimentais de nocicepção. Assim, o objetivo principal desta dissertação foi avaliar a ação anti-inflamatória do (m-CF3-PhSe)2 em modelos de inflamação aguda e subcrônica induzida por adjuvante completo de Freund (ACF) em camundongos Swiss adultos. O Comitê de Ética em Pesquisa da Universidade Federal de Santa Maria aprovou todos os procedimentos experimentais realizados no presente estudo, que são registrados sob o número 8081170317/2017. Inicialmente, foi avaliada a estabilidade físico-química do (m-CF3-PhSe)2 em diferentes condições de armazenamento. Nossos resultados demonstraram que independentemente do tempo e condições de armazenamento testadas (freezer [-20 ºC], refrigeração [4 ºC] ou temperatura ambiente [25 ºC]) não foi detectada alterações no conteúdo do composto, sugerindo uma alta estabilidade química do (m-CF3-PhSe)2. No protocolo 1, a inflamação aguda foi induzida nos camundongos por uma injeção intraplantar de ACF e 24 horas depois receberam uma única administração intragástrica (i.g.) de (m-CF3-PhSe)2. Uma curva de tempo e dose-resposta foi realizada para avaliar o efeito do (m-CF3-PhSe)2 na hipernocicepção mecânica, usando o filamento de von Frey (FVF), edema e atividade da mieloperoxidase induzida por ACF na pata. O tratamento com (m-CF3-PhSe)2 reduziu o comportamento hipernociceptivo mecânico (10 e 1 mg / kg, i.g.), bem como diminuiu o edema e a atividade da MPO na pata (10 mg / kg, i.g.). Em seguida, o protocolo 2 avaliou a efetividade de um regime de tratamento repetido com (m-CF3- PhSe)2 contra os comprometimentos inflamatórios induzidos pelo ACF em camundongos. A toxicidade potencial de tal esquema de administração também foi avaliada. Os camundongos receberam uma injeção intraplantar de ACF e 14 dias mais tarde foram tratados com (m-CF3-PhSe)2 (1 mg / kg, i.g./uma vez por dia / 10 dias). A hipernocicepção mecânica e térmica foi registrada diariamente pelo teste de FVF e teste da chapa quente (52 ºC), respectivamente. Os resultados demonstraram que a administração repetida de (m-CF3-PhSe)2 reduziu a hipernocicepção mecânica e térmica induzida pelo ACF. Além disso, o tratamento repetido com (m-CF3-PhSe)2 restaurou os compromentimentos nas alterações bioquímicas (edema e atividade da MPO na pata) e moleculares (IL-1β, TNF-α e COX-2, avaliadas em amostras de córtex cerebral contralateral) causados por ACF. Além disso, a administração repetida (m-CF3-PhSe)2 não desencadeou alterações na atividade locomotora e exploratória (número de cruzamentos, distância e velocidade média), parâmetros bioquímicos plasmáticos (função hepática, renal e cardíaca) e no estado oxidativo tecidual (fígado e rins). Coletivamente, esses dados suportam a ação anti-inflamatória do (m-CF3-PhSe)2, reforçando o potencial farmacológico do composto.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAnti-inflamatórioSelênioNocicepçãoAnti-inflammatorySeleniumNociceptionCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongosEffect of m-trifluoromethyl-diphenyl diselenide in acute and subchronic inflammatory pain model in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBrüning, César Augustohttp://lattes.cnpq.br/6471517217246368Nogueira, Cristina WayneXXXXXXXXXXXXXXXXXXXXSavegnago, LucielliXXXXXXXXXXXXXXXPrigol, MarinaXXXXXXXXXXXXXXXXXXhttp://lattes.cnpq.br/6364313853207951Araujo, Paulo Cesar de Oliveira2008000000026000e9de1c9-ec9d-42f6-a83c-64fea6966a0b2a80c561-8b12-4367-9e86-f04c42ecafd7c2b1a64f-5f22-4779-9732-0c543f42b42dcaa2f764-dc0d-42ff-9a0e-4707485ed2c2ffcb1e3e-599d-4986-a9eb-17bec777ce97reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
dc.title.alternative.eng.fl_str_mv |
Effect of m-trifluoromethyl-diphenyl diselenide in acute and subchronic inflammatory pain model in mice |
title |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
spellingShingle |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos Araujo, Paulo Cesar de Oliveira Anti-inflamatório Selênio Nocicepção Anti-inflammatory Selenium Nociception CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
title_full |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
title_fullStr |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
title_full_unstemmed |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
title_sort |
Efeito do disseleneto de m-trifluormetil difenila em modelos de dor inflamatória aguda e subcrônica em camundongos |
author |
Araujo, Paulo Cesar de Oliveira |
author_facet |
Araujo, Paulo Cesar de Oliveira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Brüning, César Augusto |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6471517217246368 |
dc.contributor.advisor-co1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor-co1Lattes.fl_str_mv |
XXXXXXXXXXXXXXXXXXXX |
dc.contributor.referee1.fl_str_mv |
Savegnago, Lucielli |
dc.contributor.referee1Lattes.fl_str_mv |
XXXXXXXXXXXXXXX |
dc.contributor.referee2.fl_str_mv |
Prigol, Marina |
dc.contributor.referee2Lattes.fl_str_mv |
XXXXXXXXXXXXXXXXXX |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6364313853207951 |
dc.contributor.author.fl_str_mv |
Araujo, Paulo Cesar de Oliveira |
contributor_str_mv |
Brüning, César Augusto Nogueira, Cristina Wayne Savegnago, Lucielli Prigol, Marina |
dc.subject.por.fl_str_mv |
Anti-inflamatório Selênio Nocicepção |
topic |
Anti-inflamatório Selênio Nocicepção Anti-inflammatory Selenium Nociception CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Anti-inflammatory Selenium Nociception |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The inflammation is a multicelular and complex process that has an essential protective role in the body. However, it can become pathological when it acts with excessive intensity and prolong endurance. In addition, the available therapeutic options to counteract inflammation has some issues regarding efficacy and safety use. In this context, the development of novel molecules with improved pharmacological profile is necessary. The m-trifluoromethyl-dyphenil diselenide [(m-CF3-PhSe)2] is an organoselenium compound that has promising biological properties, including antinociceptive action in experimental models of nociception. Thus, the main purpose of this dissertation was to evaluate the (m-CF3-PhSe)2 anti-inflammatory action in models of acute and subchronic inflammation induced by complete Freund’s adjuvant (CFA) in Swiss adult mice. The Ethical Research Committee of Federal University of Santa Maria approved all experimental procedures carried out in the present study, which are register under the number 8081170317/2017. Initially, the physicochemical stability of (m-CF3- PhSe)2 in different storage conditions was evaluated. Our results demonstrated that independent of time and storage conditions tested (freezer [-20 ºC], refrigeration [4 ºC] or room temperature [25 ºC]) no alteration in compound content was detected, suggesting a high chemical stability of (m-CF3- PhSe)2. In the protocol 1, the acute inflammation was induced in mice by an intraplantar injection of CFA and 24 h later they received a single intragastric (i.g.) administration of (m-CF3-PhSe)2. A time- and dose-response curve was performed to assess the (m-CF3-PhSe)2 effect in the mechanical hypernociception, using the von Frey hair (VFH), paw edema and myeloperoxidase activity induced by CFA. The treatment with (m-CF3-PhSe)2 reduced the mechanical hypernociceptive behavior (10 and 1 mg/kg, i.g.) as well as mitigated the paw thickness and MPO activity (10 mg/kg, i.g.). Following, the protocol 2 evaluated the effectiveness of a repeated treatment schedule with (m-CF3-PhSe)2 against the inflammatory impairments induced by CFA in mice. The potential toxicity of such administration schedule was also assessed. Mice received an intraplantar injection of CFA and 14 days later they were treated with (m-CF3-PhSe)2 (1 mg/kg, i.g./once a day/10 days). The mechanical and thermal hypernociception were daily recorded using VFH test and hot-plate test (52 ºC), respectively. The results demonstrated that the repeated administration of (m-CF3-PhSe)2 reduced both mechanical and thermal hypernociception induced by CFA. In addition, the repeated treatment with (m-CF3-PhSe)2 restored the biochemical (edema and MPO activity of paw) and molecular (IL-1β, TNF-α e COX-2, assessed in cerebral contralateral cortex samples) impairments caused by CFA. Furthermore, the repeated (m-CF3-PhSe)2 administration triggered no alteration in locomotor and exploratory activity (number of crossing, distance and average speed), plasma biochemical parameters (hepatic, renal and cardiac function) as well as in the tissue oxidative status (liver and kidneys). Collectively, these data support the (m-CF3-PhSe)2 anti-inflammatory action, reinforcing the pharmacological potential of the compound. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-02-21 |
dc.date.accessioned.fl_str_mv |
2021-05-27T18:52:14Z |
dc.date.available.fl_str_mv |
2021-05-27T18:52:14Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21004 |
url |
http://repositorio.ufsm.br/handle/1/21004 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
0e9de1c9-ec9d-42f6-a83c-64fea6966a0b 2a80c561-8b12-4367-9e86-f04c42ecafd7 c2b1a64f-5f22-4779-9732-0c543f42b42d caa2f764-dc0d-42ff-9a0e-4707485ed2c2 ffcb1e3e-599d-4986-a9eb-17bec777ce97 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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