Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Dias, Katia Cilene Ferreira
Orientador(a): Patrocínio, Silvânia Maria Mendes Vasconcelos
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:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/52837
Resumo: Schizophrenia is a chronic mental illness characterized by positive, negative and cognitive symptoms. Plants have been studied to treat Central Nervous System disorders such as an Erythrina velutina Willd. Previous studies have demonstrated neuroprotective and antioxidant activities. Here, we aimed to study the effects of the standardized extract of Erythrina velutina leaves on its behavioral, oxidative and protein expression of inflammatory mediators in the ketamine model for schizophrenia in mice. Male mice (25 g) received ketamine (KET) (25 mg/kg, i.p.) or repeated saline administration for 7 days. From day 8 to day 14 animals received Erythrina (ERYT) (100, 200 or 400 mg/kg, o.p.) or olanzapine (1 mg/kg, o.p.) 1 hour after CET administration. On the 14th day, 30 minutes after a new KET administration, we performed the open field test and the pre-pulse inhibition (PPI) tests. Afterward, all animals were euthanized and the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected to measure oxidative and nitrergic stress markers. After choosing the dose with the best behavioral effect, Western blotting was performed on the PFC for the evaluation of protein mediators of inflammation such as NFkB, Iba-1, Akt, and phospho-Akt. Our results showed that KET increased the spontaneous locomotor activity and the number of grooming of the animals when compared to the control group. KET decreased the PPI in the three pulses studied, this effect was reversed by the combination of ERYT with olanzapine. KET decreased the GSH concentration in the PFC when compared to the control group, and it was reversed by the association with ERYT in the lower doses. KET reduced the concentration of GSH in ST, this effect was reverted by ERYT at the lower dose. KET increased MDA concentration in PFC and HC compared to control groups, this effect was reversed by association with ERYT at all doses. ERYT and Olanzapine reduced the concentration of MDA in ST when compared to the KET group. The nitrite levels were decreased only in the PFC when compared to the control group, and it was reversed only by the combination with olanzapine. Decreased nitrate levels were observed in the Erythrina combination groups (ERYT 200 or 400 + KET) when compared to the control group. No alteration in the levels of Iba-1, NFkB and Akt protein expression was observed at the dose of 400mg/kg, although phosphor-Akt showed a tendency to increase. Our findings demonstrate that the standardized extract of Erythrina velutina can reduce positive and negative-like behaviors associated with schizophrenia and the oxidative stress induced by repeated doses of KET. Our study suggests a new perspective on the treatment of schizophrenia.
id UFC-7_dd646d73ce3ac64170d3a4c6231c5296
oai_identifier_str oai:repositorio.ufc.br:riufc/52837
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Dias, Katia Cilene FerreiraPatrocínio, Silvânia Maria Mendes Vasconcelos2020-07-08T13:07:49Z2020-07-08T13:07:49Z2018DIAS, Katia Cilene Ferreira. Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd. em modelo de esquizofrenia induzido por cetamina em camundongos. 2018. 69 f. Tese (Doutorado em Biotecnologia)-Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/52837Schizophrenia is a chronic mental illness characterized by positive, negative and cognitive symptoms. Plants have been studied to treat Central Nervous System disorders such as an Erythrina velutina Willd. Previous studies have demonstrated neuroprotective and antioxidant activities. Here, we aimed to study the effects of the standardized extract of Erythrina velutina leaves on its behavioral, oxidative and protein expression of inflammatory mediators in the ketamine model for schizophrenia in mice. Male mice (25 g) received ketamine (KET) (25 mg/kg, i.p.) or repeated saline administration for 7 days. From day 8 to day 14 animals received Erythrina (ERYT) (100, 200 or 400 mg/kg, o.p.) or olanzapine (1 mg/kg, o.p.) 1 hour after CET administration. On the 14th day, 30 minutes after a new KET administration, we performed the open field test and the pre-pulse inhibition (PPI) tests. Afterward, all animals were euthanized and the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected to measure oxidative and nitrergic stress markers. After choosing the dose with the best behavioral effect, Western blotting was performed on the PFC for the evaluation of protein mediators of inflammation such as NFkB, Iba-1, Akt, and phospho-Akt. Our results showed that KET increased the spontaneous locomotor activity and the number of grooming of the animals when compared to the control group. KET decreased the PPI in the three pulses studied, this effect was reversed by the combination of ERYT with olanzapine. KET decreased the GSH concentration in the PFC when compared to the control group, and it was reversed by the association with ERYT in the lower doses. KET reduced the concentration of GSH in ST, this effect was reverted by ERYT at the lower dose. KET increased MDA concentration in PFC and HC compared to control groups, this effect was reversed by association with ERYT at all doses. ERYT and Olanzapine reduced the concentration of MDA in ST when compared to the KET group. The nitrite levels were decreased only in the PFC when compared to the control group, and it was reversed only by the combination with olanzapine. Decreased nitrate levels were observed in the Erythrina combination groups (ERYT 200 or 400 + KET) when compared to the control group. No alteration in the levels of Iba-1, NFkB and Akt protein expression was observed at the dose of 400mg/kg, although phosphor-Akt showed a tendency to increase. Our findings demonstrate that the standardized extract of Erythrina velutina can reduce positive and negative-like behaviors associated with schizophrenia and the oxidative stress induced by repeated doses of KET. Our study suggests a new perspective on the treatment of schizophrenia.A esquizofrenia é um transtorno mental crônico, caracterizado por sintomas positivos, negativos e cognitivos. Apesar de ter medicamentos disponíveis na clínica, estes deixam a desejar quanto aos seus efeitos colaterais e nem todos os pacientes respondem adequadamente ao tratamento da doença. Dentro do reino vegetal, existem várias plantas que foram estudadas para tratar distúrbios do Sistema Nervoso Central, entre elas a Erythrina velutina Willd. Estudos anteriores, por exemplo, mostraram que esta planta tem ação neuroprotetora e antioxidante. O presente estudo teve como objetivo estudar os efeitos do extrato padronizado das folhas de Erythrina velutina em parâmetros comportamentais, oxidativos e na expressão proteica de fatores inflamatório no modelo de esquizofrenia induzida por cetamina. Para isso, camundongos machos (25 g) receberam administração repetida de cetamina (CET) (25 mg/kg, ip) ou salina por 7 dias. Do 8º ao 14º dia os animais receberam Erythrina (ERYT) (100, 200 ou 400 mg/kg, v.o.) ou olanzapina (1 mg/kg, v. o.) 1 hora após a administração de CET. No 14º dia, 30 minutos após a última administração de CET, foram realizados os testes de campo aberto e a inibição pré-pulso (IPP). Os animais foram sacrificados e o córtex pré-frontal (CPF), hipocampo (HC) e corpo estriado (CE) foram dissecados para os testes de estresse oxidativo e nitrérgico. Com a identificação da melhor dose, foi realizado Western Blotting do córtex pré-frontal para avaliação da expressão das seguintes proteínas relacionadas com a inflamação NFkB, Iba-1, Akt e fosfo-Akt. Os resultados mostram que CET aumentou a atividade locomotora espontânea e o número de grooming dos animais, quando comparado ao grupo controle e diminuiu o IPP nos três pulsos estudados, sendo estes efeitos revertidos pela combinação com ERYT ou olanzapina. CET diminuiu a concentração de GSH no CPF, quando comparado ao grupo controle e este efeito foi revertido pela associação com ERYT nas doses mais baixas. CET reduziu a concentração de GSH em CE e este efeito foi revertido por ERYT na dose mais baixa. CET aumentou a concentração de MDA no CPF e HC em comparação com os grupos de controle e este efeito foi revertido por associação com ERYT em todas as doses estudadas. ERYT e Olanzapina reduziram a concentração de MDA no CE, quando comparado ao grupo CET. A concentração de nitrito foi reduzida pela administração de CET apenas no PFC, quando comparado ao grupo controle e este efeito foi revertido apenas pela associação com olanzapina. A redução da concentração de nitrito no CE nos grupos associados Erythrina (ERYT 200 ou 400 + CET) foi observada quando comparada ao controle. Não foi observado na dose de 400 mg/kg nenhuma alteração nos níveis de expressão da Iba-1, NFkB e AKt, apesar da fosfo-Akt apresentar uma tendência no aumento. Nossos resultados demonstram que o extrato padronizado de Erythrina velutina pode reduzir sintomas positivos e negativos semelhantes à esquizofrenia e estresse oxidativo induzido por doses repetidas de CET. Nosso estudo sugere uma nova perspectiva para o tratamento da esquizofrenia.Erythrina velutina;Esquizofrenia;Antipsicótico;Modelo de cetamina.Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.Study of the antipsychotic effect of standardized ethanolic extract of Erythrina velutina Willd in ketamine-induced schizophrenia model in miceinfo: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/52837/10/license.txt8a4605be74aa9ea9d79846c1fba20a33MD510ORIGINAL2018_tese_kcfdias.pdf2018_tese_kcfdias.pdfapplication/pdf875357http://repositorio.ufc.br/bitstream/riufc/52837/9/2018_tese_kcfdias.pdf0c9853629644c3f21b62e1fc29fd8963MD59riufc/528372020-07-08 10:07:49.331oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-07-08T13:07:49Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
dc.title.en.pt_BR.fl_str_mv Study of the antipsychotic effect of standardized ethanolic extract of Erythrina velutina Willd in ketamine-induced schizophrenia model in mice
title Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
spellingShingle Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
Dias, Katia Cilene Ferreira
Erythrina velutina;
Esquizofrenia;
Antipsicótico;
Modelo de cetamina.
title_short Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
title_full Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
title_fullStr Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
title_full_unstemmed Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
title_sort Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd em modelo de esquizofrenia induzido por cetamina em camundongos.
author Dias, Katia Cilene Ferreira
author_facet Dias, Katia Cilene Ferreira
author_role author
dc.contributor.author.fl_str_mv Dias, Katia Cilene Ferreira
dc.contributor.advisor1.fl_str_mv Patrocínio, Silvânia Maria Mendes Vasconcelos
contributor_str_mv Patrocínio, Silvânia Maria Mendes Vasconcelos
dc.subject.por.fl_str_mv Erythrina velutina;
Esquizofrenia;
Antipsicótico;
Modelo de cetamina.
topic Erythrina velutina;
Esquizofrenia;
Antipsicótico;
Modelo de cetamina.
description Schizophrenia is a chronic mental illness characterized by positive, negative and cognitive symptoms. Plants have been studied to treat Central Nervous System disorders such as an Erythrina velutina Willd. Previous studies have demonstrated neuroprotective and antioxidant activities. Here, we aimed to study the effects of the standardized extract of Erythrina velutina leaves on its behavioral, oxidative and protein expression of inflammatory mediators in the ketamine model for schizophrenia in mice. Male mice (25 g) received ketamine (KET) (25 mg/kg, i.p.) or repeated saline administration for 7 days. From day 8 to day 14 animals received Erythrina (ERYT) (100, 200 or 400 mg/kg, o.p.) or olanzapine (1 mg/kg, o.p.) 1 hour after CET administration. On the 14th day, 30 minutes after a new KET administration, we performed the open field test and the pre-pulse inhibition (PPI) tests. Afterward, all animals were euthanized and the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected to measure oxidative and nitrergic stress markers. After choosing the dose with the best behavioral effect, Western blotting was performed on the PFC for the evaluation of protein mediators of inflammation such as NFkB, Iba-1, Akt, and phospho-Akt. Our results showed that KET increased the spontaneous locomotor activity and the number of grooming of the animals when compared to the control group. KET decreased the PPI in the three pulses studied, this effect was reversed by the combination of ERYT with olanzapine. KET decreased the GSH concentration in the PFC when compared to the control group, and it was reversed by the association with ERYT in the lower doses. KET reduced the concentration of GSH in ST, this effect was reverted by ERYT at the lower dose. KET increased MDA concentration in PFC and HC compared to control groups, this effect was reversed by association with ERYT at all doses. ERYT and Olanzapine reduced the concentration of MDA in ST when compared to the KET group. The nitrite levels were decreased only in the PFC when compared to the control group, and it was reversed only by the combination with olanzapine. Decreased nitrate levels were observed in the Erythrina combination groups (ERYT 200 or 400 + KET) when compared to the control group. No alteration in the levels of Iba-1, NFkB and Akt protein expression was observed at the dose of 400mg/kg, although phosphor-Akt showed a tendency to increase. Our findings demonstrate that the standardized extract of Erythrina velutina can reduce positive and negative-like behaviors associated with schizophrenia and the oxidative stress induced by repeated doses of KET. Our study suggests a new perspective on the treatment of schizophrenia.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2020-07-08T13:07:49Z
dc.date.available.fl_str_mv 2020-07-08T13:07:49Z
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, Katia Cilene Ferreira. Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd. em modelo de esquizofrenia induzido por cetamina em camundongos. 2018. 69 f. Tese (Doutorado em Biotecnologia)-Universidade Federal do Ceará, Fortaleza, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/52837
identifier_str_mv DIAS, Katia Cilene Ferreira. Estudo do efeito antipsicótico do extrato etanólico padronizado da Erythrina velutina Willd. em modelo de esquizofrenia induzido por cetamina em camundongos. 2018. 69 f. Tese (Doutorado em Biotecnologia)-Universidade Federal do Ceará, Fortaleza, 2018.
url http://www.repositorio.ufc.br/handle/riufc/52837
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/52837/10/license.txt
http://repositorio.ufc.br/bitstream/riufc/52837/9/2018_tese_kcfdias.pdf
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
0c9853629644c3f21b62e1fc29fd8963
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_ 1847793253534924800