EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL

Detalhes bibliográficos
Autor(a) principal: Mezzomo, Natália Fernandes
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional Universidade Franciscana
Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/986
Resumo: Schizophrenia is a serious mental illness and its pharmacological treatment consists of the administration of antipsychotics, such as haloperidol. Treatment with haloperidol often causes extrapyramidal motor disorders, such as tardive dyskinesia (TD). DT is a movement disorder characterized by involuntary movements involving the mouth, tongue and, sometimes, the limbs and trunk, and can also be studied in animal models, being called orofacial dyskinesia (DO). So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to investigate the effect of isoflavones on DO and haloperidol-induced neuroinflammation in rats, and additionally the effect of treatments on oxidative parameters. For that, male Wistar rats were treated with haloperidol decanoate (1mg / kg / day) and / or isoflavones (80 mg / kg / day) for 28 days. After 24 h of the last administration, the rats were submitted to behavioral evaluation to quantify the movements of chewing in the vacuum (MMV) and also the evaluation of the locomotor activity. Afterwards, the animals were sacrificed and the striatum was dissected and used to measure pro-inflammatory cytokines and the cortex used for the analysis of oxidative parameters. Haloperidol treatment reduced locomotor activity and increased the number of MMV, while co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of MMV. In addition, haloperidol caused a significant increase in proinflammatory cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6] and co-treatment with isoflavones was able to reduce the levels of IL -1β and TNF-α, but not IL-6. For the analyzes in cortex, there was a reduction in the levels of thiols for the group treated with haloperidol and the co-treatment with isoflavones showed no difference. However, when the levels of thiobarbituric acid reactive substances (TBARS) were measured, the haloperidol group showed a significant reduction, which was reversed by treatment with isoflavones In addition, a positive correlation was found between the levels of IL-1β and TNF-α and MMV. It is believed that the beneficial effect found with this treatment is mainly related to the potential anti-inflammatory effect of isoflavones in reducing neuroinflammation, as well as associated with its antioxidant effect.
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spelling Peroza, Luis RicardoRiesgo, Ridimar dos SantosMartins, Juliana SaibtMezzomo, Natália Fernandes2021-06-22T19:11:06Z2022-06-152021-04-30Mezzomo, Natália Fernandes. EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL. 2021. 38f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/986Schizophrenia is a serious mental illness and its pharmacological treatment consists of the administration of antipsychotics, such as haloperidol. Treatment with haloperidol often causes extrapyramidal motor disorders, such as tardive dyskinesia (TD). DT is a movement disorder characterized by involuntary movements involving the mouth, tongue and, sometimes, the limbs and trunk, and can also be studied in animal models, being called orofacial dyskinesia (DO). So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to investigate the effect of isoflavones on DO and haloperidol-induced neuroinflammation in rats, and additionally the effect of treatments on oxidative parameters. For that, male Wistar rats were treated with haloperidol decanoate (1mg / kg / day) and / or isoflavones (80 mg / kg / day) for 28 days. After 24 h of the last administration, the rats were submitted to behavioral evaluation to quantify the movements of chewing in the vacuum (MMV) and also the evaluation of the locomotor activity. Afterwards, the animals were sacrificed and the striatum was dissected and used to measure pro-inflammatory cytokines and the cortex used for the analysis of oxidative parameters. Haloperidol treatment reduced locomotor activity and increased the number of MMV, while co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of MMV. In addition, haloperidol caused a significant increase in proinflammatory cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6] and co-treatment with isoflavones was able to reduce the levels of IL -1β and TNF-α, but not IL-6. For the analyzes in cortex, there was a reduction in the levels of thiols for the group treated with haloperidol and the co-treatment with isoflavones showed no difference. However, when the levels of thiobarbituric acid reactive substances (TBARS) were measured, the haloperidol group showed a significant reduction, which was reversed by treatment with isoflavones In addition, a positive correlation was found between the levels of IL-1β and TNF-α and MMV. It is believed that the beneficial effect found with this treatment is mainly related to the potential anti-inflammatory effect of isoflavones in reducing neuroinflammation, as well as associated with its antioxidant effect.A esquizofrenia é uma doença mental grave e seu tratamento farmacológico consiste na administração de antipsicóticos, como o haloperidol. O tratamento com haloperidol frequentemente causa distúrbios motores extrapiramidais, como discinesia tardia (DT). A DT é um distúrbio do movimento caracterizado por movimentos involuntários envolvendo a boca, a língua e, às vezes, os membros e o tronco, e também podem ser estudados em modelos animais, sendo chamada de discinesia orofacial (DO). Até o momento, não existe um tratamento eficaz para a DT e alternativas têm sido buscadas. Assim, o objetivo foi investigar o efeito das isoflavonas sobre a DO e a neuroinflamação induzida por haloperidol em ratos, e adicionalmente o efeito dos tratamentos sobre parâmetros oxidativos. Para isso, ratos machos Wistar foram tratados com decanoato de haloperidol (1mg/kg/dia) e/ou isoflavonas (80 mg/kg/dia) por 28 dias. Após 24 h da última administração, os ratos foram submetidos à avaliação comportamental para quantificar os movimentos de mascar no vazio (MMV) e também a avaliação da atividade locomotora. Após, os animais foram sacrificados e o estriado foi dissecado e utilizado para dosagem de citocinas pró-inflamatórias e o córtex utilizado para análise de parâmetros oxidativos. O tratamento com haloperidol reduziu a atividade locomotora e aumentou o número de MMV, enquanto o co-tratamento com isoflavonas foi capaz de reverter a hipolocomoção e reduzir o número de MMV. Além disso, o haloperidol causou aumento significativo nas citocinas pró-inflamatórias (interleucina-1β [IL-1β], fator de necrose tumoral-α [TNF- α] e interleucina-6 [IL-6] e o co-tratamento com isoflavonas foi capaz de reduzir os níveis de IL -1β e TNF-α, mas não IL-6. Para as análises em córtex, houve uma redução dos níveis de tióis para o grupo tratado com haloperidol e o co-tratamento com isoflavonas não mostrou diferença em relação ao controle. No entanto, quando os níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS) foram mensurados, o grupo haloperidol mostrou uma redução significativa, a qual foi revertida pelo tratamento com isoflavonas. Além disso, uma correlação positiva foi encontrada entre os níveis de IL-1β e TNF- α e os MMV. Acredita-se que o efeito benéfico encontrado com esse tratamento esteja relacionado principalmente ao potencial efeito anti-inflamatório das isoflavonas em reduzir a neuroinflamação, bem como associado ao seu efeito antioxidante.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2021-06-22T19:11:06Z No. of bitstreams: 3 Dissertacao_NataliaFernandesMezzomo_VersaoParcial.pdf: 629833 bytes, checksum: 8f875ac042c1fe226b3cd2a44eeef31b (MD5) Dissertacao_NataliaFernandesMezzomo_SemAssinaturas.pdf: 1055359 bytes, checksum: b6a23e3f095e2fd75d0ba9c5377f478d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2021-06-22T19:11:06Z (GMT). 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dc.title.por.fl_str_mv EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
title EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
spellingShingle EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
Mezzomo, Natália Fernandes
Antipsicóticos. Discinesia tardia. Isoflavonas. Neuroinflamação.
Antipsychotics. Tardive dyskinesia. Isoflavones. Neuroinflammation.
Ciências da Saúde e da Vida
title_short EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
title_full EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
title_fullStr EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
title_full_unstemmed EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
title_sort EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL
author Mezzomo, Natália Fernandes
author_facet Mezzomo, Natália Fernandes
author_role author
dc.contributor.advisor1.fl_str_mv Peroza, Luis Ricardo
dc.contributor.referee1.fl_str_mv Riesgo, Ridimar dos Santos
dc.contributor.referee2.fl_str_mv Martins, Juliana Saibt
dc.contributor.author.fl_str_mv Mezzomo, Natália Fernandes
contributor_str_mv Peroza, Luis Ricardo
Riesgo, Ridimar dos Santos
Martins, Juliana Saibt
dc.subject.por.fl_str_mv Antipsicóticos. Discinesia tardia. Isoflavonas. Neuroinflamação.
topic Antipsicóticos. Discinesia tardia. Isoflavonas. Neuroinflamação.
Antipsychotics. Tardive dyskinesia. Isoflavones. Neuroinflammation.
Ciências da Saúde e da Vida
dc.subject.eng.fl_str_mv Antipsychotics. Tardive dyskinesia. Isoflavones. Neuroinflammation.
dc.subject.cnpq.fl_str_mv Ciências da Saúde e da Vida
description Schizophrenia is a serious mental illness and its pharmacological treatment consists of the administration of antipsychotics, such as haloperidol. Treatment with haloperidol often causes extrapyramidal motor disorders, such as tardive dyskinesia (TD). DT is a movement disorder characterized by involuntary movements involving the mouth, tongue and, sometimes, the limbs and trunk, and can also be studied in animal models, being called orofacial dyskinesia (DO). So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to investigate the effect of isoflavones on DO and haloperidol-induced neuroinflammation in rats, and additionally the effect of treatments on oxidative parameters. For that, male Wistar rats were treated with haloperidol decanoate (1mg / kg / day) and / or isoflavones (80 mg / kg / day) for 28 days. After 24 h of the last administration, the rats were submitted to behavioral evaluation to quantify the movements of chewing in the vacuum (MMV) and also the evaluation of the locomotor activity. Afterwards, the animals were sacrificed and the striatum was dissected and used to measure pro-inflammatory cytokines and the cortex used for the analysis of oxidative parameters. Haloperidol treatment reduced locomotor activity and increased the number of MMV, while co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of MMV. In addition, haloperidol caused a significant increase in proinflammatory cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6] and co-treatment with isoflavones was able to reduce the levels of IL -1β and TNF-α, but not IL-6. For the analyzes in cortex, there was a reduction in the levels of thiols for the group treated with haloperidol and the co-treatment with isoflavones showed no difference. However, when the levels of thiobarbituric acid reactive substances (TBARS) were measured, the haloperidol group showed a significant reduction, which was reversed by treatment with isoflavones In addition, a positive correlation was found between the levels of IL-1β and TNF-α and MMV. It is believed that the beneficial effect found with this treatment is mainly related to the potential anti-inflammatory effect of isoflavones in reducing neuroinflammation, as well as associated with its antioxidant effect.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-06-22T19:11:06Z
dc.date.issued.fl_str_mv 2021-04-30
dc.date.available.fl_str_mv 2022-06-15
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dc.identifier.citation.fl_str_mv Mezzomo, Natália Fernandes. EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL. 2021. 38f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS .
dc.identifier.uri.fl_str_mv http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/986
identifier_str_mv Mezzomo, Natália Fernandes. EFEITO DAS ISOFLAVONAS SOBRE A DISCINESIA OROFACIAL E A NEUROINFLAMAÇÃO EM RATOS TRATADOS COM HALOPERIDOL. 2021. 38f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS .
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