Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson
Ano de defesa: | 2016 |
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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 Sergipe
|
Programa de Pós-Graduação: |
Pós-Graduação em Biotecnologia (RENORBIO-SE)
|
Departamento: |
Não Informado pela instituição
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://ri.ufs.br/handle/riufs/3267 |
Resumo: | This study aimed to evaluate the antioxidant activity in vitro, as well as and the possible neuroprotective effect in vivo of the isoflavonoid formononetin (FORM) in an experimental model for the study of Parkinson's disease (PD). Among the methods used to determine the antioxidant activity of FORM in vitro, they were elected the DPPH, ABTS and FRAP. In the in vivo assays, FORM was evaluated for its biological activity on experimental PD induced by 6- hydroxydopamine (6-OHDA, 10 μg in 2 μL) injection in the right striatum. Control groups received saline containing 0.02% of ascorbic acid. The animals were subjected to the open field behavioral test after 21 days of surgery. The immunohistochemical analysis of tyrosine hydroxylase TH was performed in the substantia nigra pars compacta (SNc) and the inflammatory response was evaluated at the striatum (hystochemical for hematoxylin eosin) after sacrifice 28 days of surgery. Statistical analysis was performed by one way analysis of variance or, in the case of graduated inflammatory response, by the Kruskal-Wallis test with Dunn's extension. The in vitro results of DPPH, ABTS and FRAP showed significant antioxidant action of FORM, similar to that of the vitamins A and E (p > 0.05) and synergism between FORM and vitamin A (for equivalent vitamin C and Trolox, p < 0.001). In the open field test the rearing, crossings, ambulation (to the right and left), the immobility time and latency to onset the movement were similar between the group treated with FORM 20 mg/kg and the lesioned group and different from the groups treated with vehicle and FORM 10 mg/kg. In immunostaining for TH SNc, it was observed that 6-OHDA caused a decrease in the mean number of dopaminergic neurons (22% remaining) in the lesioned group, whereas the treatment with FORM 10 mg/kg promoted an increase to 51% and FORM 20 mg/kg in 79%, p < 0.0001. The data were also indicative of anti-inflammatory action of FORM evidenced in histopatholological analysis and by the reduction in the microglial inflammatory infiltrate. It was found that lesioned rats treated with vehicle exhibited severe grade of inflammatory response (more than 50% of the microglial infiltrate) while in the group without lesion less than 10% of inflammatory infiltrate. On the other hand, in the groups treated with FORM (10 and 20 mg/kg), there was a moderate inflammatory response, (10 to 50% infiltrate p < 0.0001). Therefore, the treatment with FORM promoted a neuroprotective and anti-inflammatory effects, which may be associated with high antioxidant activity. |
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Oliveira, Juciele Valéria Ribeiro deGomes, Margarete Zanardohttp://lattes.cnpq.br/76111765201232042017-09-25T14:06:00Z2017-09-25T14:06:00Z2016-05-30OLIVEIRA, Juciele Valéria Ribeiro de. Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson. 2016. 86 f. Tese (Pós-Graduação em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2016.https://ri.ufs.br/handle/riufs/3267This study aimed to evaluate the antioxidant activity in vitro, as well as and the possible neuroprotective effect in vivo of the isoflavonoid formononetin (FORM) in an experimental model for the study of Parkinson's disease (PD). Among the methods used to determine the antioxidant activity of FORM in vitro, they were elected the DPPH, ABTS and FRAP. In the in vivo assays, FORM was evaluated for its biological activity on experimental PD induced by 6- hydroxydopamine (6-OHDA, 10 μg in 2 μL) injection in the right striatum. Control groups received saline containing 0.02% of ascorbic acid. The animals were subjected to the open field behavioral test after 21 days of surgery. The immunohistochemical analysis of tyrosine hydroxylase TH was performed in the substantia nigra pars compacta (SNc) and the inflammatory response was evaluated at the striatum (hystochemical for hematoxylin eosin) after sacrifice 28 days of surgery. Statistical analysis was performed by one way analysis of variance or, in the case of graduated inflammatory response, by the Kruskal-Wallis test with Dunn's extension. The in vitro results of DPPH, ABTS and FRAP showed significant antioxidant action of FORM, similar to that of the vitamins A and E (p > 0.05) and synergism between FORM and vitamin A (for equivalent vitamin C and Trolox, p < 0.001). In the open field test the rearing, crossings, ambulation (to the right and left), the immobility time and latency to onset the movement were similar between the group treated with FORM 20 mg/kg and the lesioned group and different from the groups treated with vehicle and FORM 10 mg/kg. In immunostaining for TH SNc, it was observed that 6-OHDA caused a decrease in the mean number of dopaminergic neurons (22% remaining) in the lesioned group, whereas the treatment with FORM 10 mg/kg promoted an increase to 51% and FORM 20 mg/kg in 79%, p < 0.0001. The data were also indicative of anti-inflammatory action of FORM evidenced in histopatholological analysis and by the reduction in the microglial inflammatory infiltrate. It was found that lesioned rats treated with vehicle exhibited severe grade of inflammatory response (more than 50% of the microglial infiltrate) while in the group without lesion less than 10% of inflammatory infiltrate. On the other hand, in the groups treated with FORM (10 and 20 mg/kg), there was a moderate inflammatory response, (10 to 50% infiltrate p < 0.0001). Therefore, the treatment with FORM promoted a neuroprotective and anti-inflammatory effects, which may be associated with high antioxidant activity.Considerando a demanda de tratamentos efetivos para prevenção e tratamento da doença de Parkinson (DP) e o papel do estresse oxidativo em desordens neurológicas e neurodegenerativas, o presente trabalho teve por objetivo avaliar a atividade antioxidante in vitro, bem como a possível ação neuroprotetora in vivo do isoflavonóide formononetina (FORM) em modelo experimental para estudo da DP. Dentre os métodos usados para determinar a atividade antioxidante da FORM in vitro, foram eleitos o DPPH, o ABTS e o FRAP. Em ensaios in vivo, foi avaliada sua atividade biológica frente à lesão da via nigroestriatal causada por 6- hidroxidopamina (6-OHDA, 10 μg em 2 μL), com o lado direito utilizado como parâmetro para microinjeção no estriado. Animais controle receberam solução salina contendo 0,02% de ácido ascórbico. Os animais foram submetidos a teste comportamental de campo aberto, 21 dias após a cirurgia e procedeu-se à análise imunohistoquímica para a enzima tirosina hidroxilase (TH) e análise histoquímica (hematoxilina eosina) para avaliação de alterações estruturais e da resposta inflamatória, no estriado e na substância negra compacta (SNc), após eutanásia aos 28 dias. Os dados foram submetidos à análise de variância de uma via (ANOVA) seguida do pósteste de Tukey, à exceção do escore da resposta inflamatória, que foi analisado por meio de Teste Kruskal-Wallis, com extensão de Dunn. Nos resultados in vitro, através dos testes DPPH, ABTS e FRAP encontrou-se ação antioxidante de FORM semelhante à das vitaminas A e E e sinergismo entre a FORM e a vitamina A (por Equivalente de vitamina C e Trolox, p < 0,001). Nos resultados in vivo, para os testes de comportamento em campo aberto, foram avaliados os parâmetros de elevações (rearing), explorações (crossing), ambulações para a direita e esquerda, o tempo de imobilidade e de latência para início do movimento, sendo os resultados do grupo tratado com FORM a 20 mg/kg semelhantes aos do grupo não lesionado e diferentes dos grupos lesionados tratados com veículo e FORM a 10 mg/kg. Na imunomarcação para TH na SNc, a 6-OHDA promoveu diminuição de neurônios, ficando remanescentes em média 22% no grupo lesionado e tratados com veículo, enquanto que o tratamento com FORM a 10 mg/kg promoveu aumento do número médio em 51% e o tratamento com FORM a 20 mg/kg em 79%. Os dados foram indicativos também de efeito anti-inflamatório da FORM, evidenciada na análise de infiltrado inflamatório microglial. Verificou-se que animais lesionados e tratados com veículo apresentaram grau severo de inflamação (mais de 50% de infiltrado inflamatório), o grupo controle apresentou menos de 10% de infiltrado inflamatório, enquanto nos grupos tratados com FORM (10 e 20 mg/kg) observou-se grau moderado de inflamação (10 a 50% de infiltrado p < 0,0001). Portanto, o tratamento com a FORM promoveu aumento na sobrevivência de neurônios dopaminérgicos e diminui a resposta inflamatória no estriado, efeitos que podem estar associados a sua atividade antioxidante.application/pdfporUniversidade Federal de SergipePós-Graduação em Biotecnologia (RENORBIO-SE)UFSBrasilBiotecnologiaBiotecnologia farmacêuticaDoença de ParkinsonAntioxidantesFormononetinaIsoflavonasAgentes anti-inflamatóriosAgentes neuroprotetoresNeuroproteçãoFlavonoidsAnti-inflammatory agentsAntioxidantsNerve degenerationCIENCIAS BIOLOGICASEfeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinsoninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSORIGINALJUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdfapplication/pdf3760289https://ri.ufs.br/jspui/bitstream/riufs/3267/1/JUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf457e63970b14706deb48f78d9770730fMD51TEXTJUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.txtJUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.txtExtracted texttext/plain139908https://ri.ufs.br/jspui/bitstream/riufs/3267/2/JUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.txt67d16a1e033c31446ee15551fa224972MD52THUMBNAILJUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.jpgJUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.jpgGenerated Thumbnailimage/jpeg1378https://ri.ufs.br/jspui/bitstream/riufs/3267/3/JUCIELE_VALERIA_RIBEIRO_OLIVEIRA.pdf.jpgfb2d5cc1266b60c30699bc668f7474f8MD53riufs/32672024-01-17 17:02:59.301oai:ufs.br:riufs/3267Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2024-01-17T20:02:59Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.por.fl_str_mv |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
title |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
spellingShingle |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson Oliveira, Juciele Valéria Ribeiro de Biotecnologia Biotecnologia farmacêutica Doença de Parkinson Antioxidantes Formononetina Isoflavonas Agentes anti-inflamatórios Agentes neuroprotetores Neuroproteção Flavonoids Anti-inflammatory agents Antioxidants Nerve degeneration CIENCIAS BIOLOGICAS |
title_short |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
title_full |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
title_fullStr |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
title_full_unstemmed |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
title_sort |
Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson |
author |
Oliveira, Juciele Valéria Ribeiro de |
author_facet |
Oliveira, Juciele Valéria Ribeiro de |
author_role |
author |
dc.contributor.author.fl_str_mv |
Oliveira, Juciele Valéria Ribeiro de |
dc.contributor.advisor1.fl_str_mv |
Gomes, Margarete Zanardo |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7611176520123204 |
contributor_str_mv |
Gomes, Margarete Zanardo |
dc.subject.por.fl_str_mv |
Biotecnologia Biotecnologia farmacêutica Doença de Parkinson Antioxidantes Formononetina Isoflavonas Agentes anti-inflamatórios Agentes neuroprotetores Neuroproteção Flavonoids Anti-inflammatory agents Antioxidants |
topic |
Biotecnologia Biotecnologia farmacêutica Doença de Parkinson Antioxidantes Formononetina Isoflavonas Agentes anti-inflamatórios Agentes neuroprotetores Neuroproteção Flavonoids Anti-inflammatory agents Antioxidants Nerve degeneration CIENCIAS BIOLOGICAS |
dc.subject.eng.fl_str_mv |
Nerve degeneration |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS |
description |
This study aimed to evaluate the antioxidant activity in vitro, as well as and the possible neuroprotective effect in vivo of the isoflavonoid formononetin (FORM) in an experimental model for the study of Parkinson's disease (PD). Among the methods used to determine the antioxidant activity of FORM in vitro, they were elected the DPPH, ABTS and FRAP. In the in vivo assays, FORM was evaluated for its biological activity on experimental PD induced by 6- hydroxydopamine (6-OHDA, 10 μg in 2 μL) injection in the right striatum. Control groups received saline containing 0.02% of ascorbic acid. The animals were subjected to the open field behavioral test after 21 days of surgery. The immunohistochemical analysis of tyrosine hydroxylase TH was performed in the substantia nigra pars compacta (SNc) and the inflammatory response was evaluated at the striatum (hystochemical for hematoxylin eosin) after sacrifice 28 days of surgery. Statistical analysis was performed by one way analysis of variance or, in the case of graduated inflammatory response, by the Kruskal-Wallis test with Dunn's extension. The in vitro results of DPPH, ABTS and FRAP showed significant antioxidant action of FORM, similar to that of the vitamins A and E (p > 0.05) and synergism between FORM and vitamin A (for equivalent vitamin C and Trolox, p < 0.001). In the open field test the rearing, crossings, ambulation (to the right and left), the immobility time and latency to onset the movement were similar between the group treated with FORM 20 mg/kg and the lesioned group and different from the groups treated with vehicle and FORM 10 mg/kg. In immunostaining for TH SNc, it was observed that 6-OHDA caused a decrease in the mean number of dopaminergic neurons (22% remaining) in the lesioned group, whereas the treatment with FORM 10 mg/kg promoted an increase to 51% and FORM 20 mg/kg in 79%, p < 0.0001. The data were also indicative of anti-inflammatory action of FORM evidenced in histopatholological analysis and by the reduction in the microglial inflammatory infiltrate. It was found that lesioned rats treated with vehicle exhibited severe grade of inflammatory response (more than 50% of the microglial infiltrate) while in the group without lesion less than 10% of inflammatory infiltrate. On the other hand, in the groups treated with FORM (10 and 20 mg/kg), there was a moderate inflammatory response, (10 to 50% infiltrate p < 0.0001). Therefore, the treatment with FORM promoted a neuroprotective and anti-inflammatory effects, which may be associated with high antioxidant activity. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-05-30 |
dc.date.accessioned.fl_str_mv |
2017-09-25T14:06:00Z |
dc.date.available.fl_str_mv |
2017-09-25T14:06:00Z |
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 |
OLIVEIRA, Juciele Valéria Ribeiro de. Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson. 2016. 86 f. Tese (Pós-Graduação em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2016. |
dc.identifier.uri.fl_str_mv |
https://ri.ufs.br/handle/riufs/3267 |
identifier_str_mv |
OLIVEIRA, Juciele Valéria Ribeiro de. Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson. 2016. 86 f. Tese (Pós-Graduação em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2016. |
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