3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos
Ano de defesa: | 2014 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/4478 |
Resumo: | Selenophenes are a promising class of heterocyclic selenium-containing compounds presenting important pharmacological properties. Based on selenium well-described role on mood regulation and since depression is a serious and prevalent disease affecting a wide part of the world s population, the main aim of this work was to investigate de antidepressant-like action of 3-(organosseleno)-2,5-diphenyl-selenophenes in mice. The pharmacological effect of these compounds was analyzed by using different experimental models of depression and results were shown by three scientific articles. Firstly, results of Article 1 demonstrated the antidepressant-like action of five selenophene compounds. H-DPS, CH3-DPS, Cl-DPS, FDPS and CF3-DPS reduced the total immobility time of mice evaluated in the forced swimming test (FST), which seems to be related to their chemical structure. The antidepressant-like action of F-DPS was observed at lower doses than other selenophenes e involves the phosphorylation of extracellular-signal-regulated kinases (ERK), whose signaling pathway is commonly modulated by antidepressant drugs. Articles 2 and 3 investigated the pharmacological effect of F-DPS in mouse models of depression induced by both neuropathic pain and chronic corticosterone administration, respectively. Both the acute and subchronic treatments with F-DPS significantly reversed the depression-related behavior produced by partial sciatic nerve ligation (PSNL), whereas pain sensibility was only reduced after repeated treatment with this selenophene. Besides, repeated administration of the glucocorticoid hormone corticosterone induced behavior, endocrinal and neurochemical changes similar to those clinically observed in depression, which were also reversed by treatment of animals with F-DPS. Based on these data, the mechanisms of pharmacological action of this organoselenium compound seem to involve, at least in part, a modulation of glutamatergic and serotonergic systems, the hypothalamic-pituitary-adrenal (HPA) axis regulation and changes on neuronal pathways related to the synaptic plasticity. Together, the results shown in this thesis suggest the pharmacological properties of selenophene compounds, particularly F-DPS, as an interesting tool in the study and development of future therapies for depressive disorders. |
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2014-11-122014-11-122014-03-11GAI, Bibiana Mozzaquatro. 2,5-Diphenyl-3-(4-fluorophenylseleno) selenophene produces antidepressant-like action in different models of depression in mice. 2014. 132 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/4478Selenophenes are a promising class of heterocyclic selenium-containing compounds presenting important pharmacological properties. Based on selenium well-described role on mood regulation and since depression is a serious and prevalent disease affecting a wide part of the world s population, the main aim of this work was to investigate de antidepressant-like action of 3-(organosseleno)-2,5-diphenyl-selenophenes in mice. The pharmacological effect of these compounds was analyzed by using different experimental models of depression and results were shown by three scientific articles. Firstly, results of Article 1 demonstrated the antidepressant-like action of five selenophene compounds. H-DPS, CH3-DPS, Cl-DPS, FDPS and CF3-DPS reduced the total immobility time of mice evaluated in the forced swimming test (FST), which seems to be related to their chemical structure. The antidepressant-like action of F-DPS was observed at lower doses than other selenophenes e involves the phosphorylation of extracellular-signal-regulated kinases (ERK), whose signaling pathway is commonly modulated by antidepressant drugs. Articles 2 and 3 investigated the pharmacological effect of F-DPS in mouse models of depression induced by both neuropathic pain and chronic corticosterone administration, respectively. Both the acute and subchronic treatments with F-DPS significantly reversed the depression-related behavior produced by partial sciatic nerve ligation (PSNL), whereas pain sensibility was only reduced after repeated treatment with this selenophene. Besides, repeated administration of the glucocorticoid hormone corticosterone induced behavior, endocrinal and neurochemical changes similar to those clinically observed in depression, which were also reversed by treatment of animals with F-DPS. Based on these data, the mechanisms of pharmacological action of this organoselenium compound seem to involve, at least in part, a modulation of glutamatergic and serotonergic systems, the hypothalamic-pituitary-adrenal (HPA) axis regulation and changes on neuronal pathways related to the synaptic plasticity. Together, the results shown in this thesis suggest the pharmacological properties of selenophene compounds, particularly F-DPS, as an interesting tool in the study and development of future therapies for depressive disorders.Os selenofenos são uma classe de compostos heterocíclicos aromáticos com promissoras propriedades farmacológicas. Tendo em vista o importante papel do selênio na regulação do humor e a grande prevalência populacional das doenças depressivas, o principal objetivo deste estudo foi investigar a ação do tipo antidepressiva de 3-(organosseleno)-2,5-difenilselenofenos em camundongos. A fim de atender a este objetivo, o efeito farmacológico destes compostos foi analisado pelo uso de diferentes modelos experimentais de depressão e os resultados foram apresentados em três artigos científicos. Primeiramente, os resultados do Artigo 1 demonstraram a ação do tipo antidepressiva de cinco representantes da classe dos selenofenos. Os compostos H-DPS, CH3-DPS, Cl-DPS, F-DPS e CF3-DPS reduziram significantemente o tempo total de imobilidade de camundongos avaliados no teste do nado forçado (TNF), efeito este que parece estar relacionado às suas estruturas químicas. A ação do tipo antidepressiva do F-DPS foi observada em menores doses em comparação aos outros selenofenos e envolve a fosforilação da proteína quinase regulada por sinal extracelular (ERK), cuja via de sinalização é comumente modulada por drogas antidepressivas. Os Artigos 2 e 3 investigaram o efeito farmacológico do F-DPS em modelos crônicos de depressão induzida pela dor neuropática e pela administração crônica de corticosterona em camundongos, respectivamente. Tanto o tratamento agudo como o subcrônico com F-DPS reverteram significantemente o comportamento do tipo depressivo produzido pela ligação parcial do nervo ciático (LPNC), enquanto que a sensibilidade à dor foi reduzida somente após a terapia prolongada com este composto. Por sua vez, a administração repetida do hormônio glicocorticoide corticosterona induziu alterações comportamentais, endócrinas e neuroquímicas similares às observadas clinicamente na depressão e que também foram revertidas pelo tratamento dos animais com F-DPS. Com base nestes resultados, acredita-se que os mecanismos de ação farmacológica deste composto orgânico de selênio envolvam, pelo menos em parte, a modulação dos sistemas glutamatérgico e serotonérgico, a regulação da atividade do eixo hipotálamo-pituitária-adrenal (HPA) e modificações em vias neuronais relacionadas à plasticidade sináptica. Juntos os resultados apresentados nesta tese de doutorado sugerem que o estudo das propriedades farmacológicas de compostos selenofenos, particularmente do F-DPS, parece ser interessante no desenvolvimento de futuras terapias para o tratamento dos distúrbios neurológicos relacionados às doenças depressivas.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaSelênioSelenofenosDepressãoEstresseDor crônicaCamundongosSeleniumSelenophenesDepressionStressChronic painMiceCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos2,5-Diphenyl-3-(4-fluorophenylseleno) selenophene produces antidepressant-like action in different models of depression in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Rodrigues, Ana Lúcia Severohttp://lattes.cnpq.br/0223274024436216Ferreira, Julianohttp://lattes.cnpq.br/2694197910478313Savegnago, Luciellihttp://lattes.cnpq.br/1480751214999787Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413http://lattes.cnpq.br/4903325870217874Gai, Bibiana Mozzaquatro2008000000024005003005005005005000186436d-f662-4a5e-b36e-8c8ab8e10bf8fca66c0c-dee5-4e07-8c10-06229de2443851038c1d-713d-4890-ac1c-4cdcedeba73bb410c4c0-c1c6-41df-aed8-741731a2b8a2e562a88b-5d35-4dc2-b392-f3e2cb780dbdfef98c94-2404-4764-a10c-561dd9b55f47info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALGAI, BIBIANA MOZZAQUATRO.pdfTese de Doutoradoapplication/pdf13444686http://repositorio.ufsm.br/bitstream/1/4478/1/GAI%2c%20BIBIANA%20MOZZAQUATRO.pdf72ea9739c9ea3cee9991b3fa47cabeb5MD51TEXTGAI, BIBIANA MOZZAQUATRO.pdf.txtGAI, BIBIANA MOZZAQUATRO.pdf.txtExtracted texttext/plain210443http://repositorio.ufsm.br/bitstream/1/4478/2/GAI%2c%20BIBIANA%20MOZZAQUATRO.pdf.txt978eb90324e5687ba995bda4af38a099MD52THUMBNAILGAI, BIBIANA MOZZAQUATRO.pdf.jpgGAI, BIBIANA MOZZAQUATRO.pdf.jpgIM Thumbnailimage/jpeg5245http://repositorio.ufsm.br/bitstream/1/4478/3/GAI%2c%20BIBIANA%20MOZZAQUATRO.pdf.jpg0068b3261e1e95a98348fc99c895e8bdMD531/44782022-07-21 14:48:02.168oai:repositorio.ufsm.br:1/4478Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-07-21T17:48:02Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
dc.title.alternative.eng.fl_str_mv |
2,5-Diphenyl-3-(4-fluorophenylseleno) selenophene produces antidepressant-like action in different models of depression in mice |
title |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
spellingShingle |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos Gai, Bibiana Mozzaquatro Selênio Selenofenos Depressão Estresse Dor crônica Camundongos Selenium Selenophenes Depression Stress Chronic pain Mice CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
title_full |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
title_fullStr |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
title_full_unstemmed |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
title_sort |
3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos |
author |
Gai, Bibiana Mozzaquatro |
author_facet |
Gai, Bibiana Mozzaquatro |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Rodrigues, Ana Lúcia Severo |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0223274024436216 |
dc.contributor.referee2.fl_str_mv |
Ferreira, Juliano |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/2694197910478313 |
dc.contributor.referee3.fl_str_mv |
Savegnago, Lucielli |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/1480751214999787 |
dc.contributor.referee4.fl_str_mv |
Burger, Marilise Escobar |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9128090974948413 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4903325870217874 |
dc.contributor.author.fl_str_mv |
Gai, Bibiana Mozzaquatro |
contributor_str_mv |
Nogueira, Cristina Wayne Rodrigues, Ana Lúcia Severo Ferreira, Juliano Savegnago, Lucielli Burger, Marilise Escobar |
dc.subject.por.fl_str_mv |
Selênio Selenofenos Depressão Estresse Dor crônica Camundongos |
topic |
Selênio Selenofenos Depressão Estresse Dor crônica Camundongos Selenium Selenophenes Depression Stress Chronic pain Mice CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Selenium Selenophenes Depression Stress Chronic pain Mice |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Selenophenes are a promising class of heterocyclic selenium-containing compounds presenting important pharmacological properties. Based on selenium well-described role on mood regulation and since depression is a serious and prevalent disease affecting a wide part of the world s population, the main aim of this work was to investigate de antidepressant-like action of 3-(organosseleno)-2,5-diphenyl-selenophenes in mice. The pharmacological effect of these compounds was analyzed by using different experimental models of depression and results were shown by three scientific articles. Firstly, results of Article 1 demonstrated the antidepressant-like action of five selenophene compounds. H-DPS, CH3-DPS, Cl-DPS, FDPS and CF3-DPS reduced the total immobility time of mice evaluated in the forced swimming test (FST), which seems to be related to their chemical structure. The antidepressant-like action of F-DPS was observed at lower doses than other selenophenes e involves the phosphorylation of extracellular-signal-regulated kinases (ERK), whose signaling pathway is commonly modulated by antidepressant drugs. Articles 2 and 3 investigated the pharmacological effect of F-DPS in mouse models of depression induced by both neuropathic pain and chronic corticosterone administration, respectively. Both the acute and subchronic treatments with F-DPS significantly reversed the depression-related behavior produced by partial sciatic nerve ligation (PSNL), whereas pain sensibility was only reduced after repeated treatment with this selenophene. Besides, repeated administration of the glucocorticoid hormone corticosterone induced behavior, endocrinal and neurochemical changes similar to those clinically observed in depression, which were also reversed by treatment of animals with F-DPS. Based on these data, the mechanisms of pharmacological action of this organoselenium compound seem to involve, at least in part, a modulation of glutamatergic and serotonergic systems, the hypothalamic-pituitary-adrenal (HPA) axis regulation and changes on neuronal pathways related to the synaptic plasticity. Together, the results shown in this thesis suggest the pharmacological properties of selenophene compounds, particularly F-DPS, as an interesting tool in the study and development of future therapies for depressive disorders. |
publishDate |
2014 |
dc.date.accessioned.fl_str_mv |
2014-11-12 |
dc.date.available.fl_str_mv |
2014-11-12 |
dc.date.issued.fl_str_mv |
2014-03-11 |
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 |
GAI, Bibiana Mozzaquatro. 2,5-Diphenyl-3-(4-fluorophenylseleno) selenophene produces antidepressant-like action in different models of depression in mice. 2014. 132 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4478 |
identifier_str_mv |
GAI, Bibiana Mozzaquatro. 2,5-Diphenyl-3-(4-fluorophenylseleno) selenophene produces antidepressant-like action in different models of depression in mice. 2014. 132 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
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http://repositorio.ufsm.br/handle/1/4478 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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UFSM |
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