Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Venâncio, Edith Teles
Orientador(a): Fonteles , Marta Maria de França
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/15739
Resumo: Epilepsy affects about 50 million people and 30% of these people have refractory seizures to the treatment available. The mechanism of seizure involves alteration in neurotransmitters and amino acids, oxidative stress, excitotoxicity and neuronal injury. The standardized extract of Chamba (CH), prepared from the aerial parts of Justicia pectoralis, presented in previous studies anxiolytic effect related to the upregulation of GABA/benzodiazepine receptors. Thus, with the aim to investigate the anticonvulsant potential of Chamba and its mechanism of action, we performed seizure models induced by picrotoxin, strychnine, electroshock and pilocarpine. To evaluate the antioxidant activity, we measured levels of lipid peroxidation, nitrite and catalase activity in hippocampus, striatum and marrow (strychnine model) in the seizure models mentioned above. Next, we determined the levels of inhibitory amino acid (GABA, glycine, and taurine) and excitatory amino acid (glutamate and aspartate) in the hippocampus after pilocarpine seizure and, to verify neuroprotective activity, we also evaluated the percentage of neuronal damage in the CA1 and CA3 fields of hippocampus after status epilepticus induced by pilocarpine. Swiss female mice were treated orally (gavage) and divided into groups according to the study, among them: anticonvulsant activity [6 groups (n = 10): control (distilled water); CH (25, 50 and 100 mg/kg); Phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], antioxidant activity [4 groups (n = 10): control (distilled water), CH (50 mg/kg), phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], determination of the amino acid levels [3 groups (n = 8): control (distilled water), CH (50 mg/kg) and phenobarbital (10 mg/kg)] and verification of neuronal damage [3 groups (n = 4): control (distilled water), CH (50 mg/kg) or pilocarpine (400mg/kg, intraperitoneally). The results showed that CHAMBA presented a anticonvulsant effect because it increased latency of first convulsion and latency to death parameters in all models and doses used, except the dose of 25 mg/kg, that was not significant in picrotoxin model. The evaluation of the antioxidant activity showed that Chamba reduced levels of lipid peroxidation and nitrite, and increased catalase activity in hippocampus and striatum in all models used. The determination of amino acid levels showed that Chamba increased levels of inhibitory amino acids, and reduced levels of excitatory amino acids and, finally, the evaluation of the neuroprotective activity by the percentage of neuronal damage, Chamba showed a reduced neuronal damage in the CA1 and CA3 areas of the hippocampus. In conclusion, the study suggests a modulating action carried out by the standardized extract of Justicia pectoralis on seizures by altering levels of neurotransmitters, amino acids, oxidative stress and neuronal damage, which are the mechanisms involved in the pathology.
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spelling Venâncio, Edith TelesFonteles , Marta Maria de França2016-03-28T13:00:35Z2016-03-28T13:00:35Z2015-01-30VENÂNCIO, E. T. Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação. 2015. 184 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.http://www.repositorio.ufc.br/handle/riufc/15739Epilepsy affects about 50 million people and 30% of these people have refractory seizures to the treatment available. The mechanism of seizure involves alteration in neurotransmitters and amino acids, oxidative stress, excitotoxicity and neuronal injury. The standardized extract of Chamba (CH), prepared from the aerial parts of Justicia pectoralis, presented in previous studies anxiolytic effect related to the upregulation of GABA/benzodiazepine receptors. Thus, with the aim to investigate the anticonvulsant potential of Chamba and its mechanism of action, we performed seizure models induced by picrotoxin, strychnine, electroshock and pilocarpine. To evaluate the antioxidant activity, we measured levels of lipid peroxidation, nitrite and catalase activity in hippocampus, striatum and marrow (strychnine model) in the seizure models mentioned above. Next, we determined the levels of inhibitory amino acid (GABA, glycine, and taurine) and excitatory amino acid (glutamate and aspartate) in the hippocampus after pilocarpine seizure and, to verify neuroprotective activity, we also evaluated the percentage of neuronal damage in the CA1 and CA3 fields of hippocampus after status epilepticus induced by pilocarpine. Swiss female mice were treated orally (gavage) and divided into groups according to the study, among them: anticonvulsant activity [6 groups (n = 10): control (distilled water); CH (25, 50 and 100 mg/kg); Phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], antioxidant activity [4 groups (n = 10): control (distilled water), CH (50 mg/kg), phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], determination of the amino acid levels [3 groups (n = 8): control (distilled water), CH (50 mg/kg) and phenobarbital (10 mg/kg)] and verification of neuronal damage [3 groups (n = 4): control (distilled water), CH (50 mg/kg) or pilocarpine (400mg/kg, intraperitoneally). The results showed that CHAMBA presented a anticonvulsant effect because it increased latency of first convulsion and latency to death parameters in all models and doses used, except the dose of 25 mg/kg, that was not significant in picrotoxin model. The evaluation of the antioxidant activity showed that Chamba reduced levels of lipid peroxidation and nitrite, and increased catalase activity in hippocampus and striatum in all models used. The determination of amino acid levels showed that Chamba increased levels of inhibitory amino acids, and reduced levels of excitatory amino acids and, finally, the evaluation of the neuroprotective activity by the percentage of neuronal damage, Chamba showed a reduced neuronal damage in the CA1 and CA3 areas of the hippocampus. In conclusion, the study suggests a modulating action carried out by the standardized extract of Justicia pectoralis on seizures by altering levels of neurotransmitters, amino acids, oxidative stress and neuronal damage, which are the mechanisms involved in the pathology.A epilepsia acomete cerca de 50 milhões de pessoas e 30 % destas apresentam crises refratárias ao tratamento disponível no mercado. O mecanismo da convulsão envolve alteração de neurotransmissores e aminoácidos, estresse oxidativo, excitotoxicidade e lesão neuronal. O extrato padronizado de chambá (CH), preparado a partir das partes aéreas da Justicia pectoralis, apresentou em estudos prévios, efeito ansiolítico relacionado à modulação positiva dos receptores GABAA/benzodiazepínicos. Dessa forma, objetivando investigar o potencial anticonvulsivante do chambá, bem como o mecanismo de ação, foram realizados modelos de convulsão induzida por picrotoxina, estricnina, eletrochoque e pilocarpina. Para avaliar a atividade antioxidante através do envolvimento do estresse oxidativo foram mensurados os níveis de peroxidação lipídica, nitrito e a atividade da catalase em hipocampo, corpo estriado e medula (modelo de estricnina) nos modelos de convulsão mencionados acima. Em seguida, foram determinados os níveis de aminoácidos inibitórios (GABA, glicina e taurina) e excitatórios (glutamato e aspartato) no hipocampo após convulsão por pilocarpina e, para verificar a atividade neuroprotetora foram avaliadas a porcentagem de danos neuronais nas áreas CA1 e CA3 do hipocampo após status epilepticus induzido por pilocarpina. Foram utilizados camundongos Swiss fêmeas, tratados por via oral (gavage) e divididos em grupos de acordo com estudo realizado, dentre eles: atividade anticonvulsivante [6 grupos (n=10): controle (água destilada); CH (25, 50 e 100 mg/Kg); Fenobarbital (10 mg/Kg) ou Oxcarbazepina (60 mg/Kg)], atividade antioxidante [4 grupos (n=10): controle (água destilada), CH (50 mg/Kg), fenobarbital (10 mg/Kg) ou Oxcarbazepina (60 mg/Kg)], determinação da atividade sobre os níveis de aminoácidos [3 grupos (n=8): controle (água destilada), CH (50 mg/Kg) ou fenobarbital (10 mg/Kg)] e para verificação dos danos neuronais [3 grupos (n=4): controle (água destilada), CH (50 mg/Kg) ou pilocarpina (400 mg/Kg, via intraperitoneal). Os resultados mostraram que o chambá apresentou efeito anticonvulsivante, pois aumentou os parâmetros latência para 1° convulsão e latência para morte em todos os modelos e nas doses utilizadas, exceto a dose de 25 mg/Kg que não foi significativa no modelo de picrotoxina. A avaliação da atividade antioxidante mostrou que o chambá reduziu os níveis de peroxidação lipídica e nitrito, e aumentou a atividade da catalase no hipocampo e corpo estriado em todos os modelos utilizados. A determinação dos níveis de aminoácidos mostrou que o chambá aumentou os níveis dos aminoácidos inibitórios e reduziu os níveis dos aminoácidos excitatórios e, por fim, a avaliação da atividade neuroprotetora através da porcentagem de danos neuronais mostrou que o chambá reduziu as lesões neuronais nas áreas CA1 e CA3 do hipocampo. Em conclusão, o estudo sugere uma ação moduladora, exercida pelo extrato padronizado de Justicia pectoralis, sobre a convulsão através da alteração dos níveis de neurotransmissores, aminoácidos, estresse oxidativo e danos neuronais, sendo estes, mecanismos envolvidos na patologia.Medicamentos FitoterápicosEpilepsiaAntioxidantesFármacos NeuroprotetoresAvaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de açãoAssessment of anticonvulsant’s potential of standardized extract of Justicia pectoralis (Chamba): neuroprotection study and mechanism of actioninfo: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/openAccessORIGINAL2015_tese_etvenancio.pdf2015_tese_etvenancio.pdfapplication/pdf1882606http://repositorio.ufc.br/bitstream/riufc/15739/1/2015_tese_etvenancio.pdfcd82ce777cfd954cc105364f79bf736dMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81786http://repositorio.ufc.br/bitstream/riufc/15739/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52riufc/157392019-10-24 08:45:14.754oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-24T11:45:14Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
dc.title.en.pt_BR.fl_str_mv Assessment of anticonvulsant’s potential of standardized extract of Justicia pectoralis (Chamba): neuroprotection study and mechanism of action
title Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
spellingShingle Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
Venâncio, Edith Teles
Medicamentos Fitoterápicos
Epilepsia
Antioxidantes
Fármacos Neuroprotetores
title_short Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
title_full Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
title_fullStr Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
title_full_unstemmed Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
title_sort Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação
author Venâncio, Edith Teles
author_facet Venâncio, Edith Teles
author_role author
dc.contributor.author.fl_str_mv Venâncio, Edith Teles
dc.contributor.advisor1.fl_str_mv Fonteles , Marta Maria de França
contributor_str_mv Fonteles , Marta Maria de França
dc.subject.por.fl_str_mv Medicamentos Fitoterápicos
Epilepsia
Antioxidantes
Fármacos Neuroprotetores
topic Medicamentos Fitoterápicos
Epilepsia
Antioxidantes
Fármacos Neuroprotetores
description Epilepsy affects about 50 million people and 30% of these people have refractory seizures to the treatment available. The mechanism of seizure involves alteration in neurotransmitters and amino acids, oxidative stress, excitotoxicity and neuronal injury. The standardized extract of Chamba (CH), prepared from the aerial parts of Justicia pectoralis, presented in previous studies anxiolytic effect related to the upregulation of GABA/benzodiazepine receptors. Thus, with the aim to investigate the anticonvulsant potential of Chamba and its mechanism of action, we performed seizure models induced by picrotoxin, strychnine, electroshock and pilocarpine. To evaluate the antioxidant activity, we measured levels of lipid peroxidation, nitrite and catalase activity in hippocampus, striatum and marrow (strychnine model) in the seizure models mentioned above. Next, we determined the levels of inhibitory amino acid (GABA, glycine, and taurine) and excitatory amino acid (glutamate and aspartate) in the hippocampus after pilocarpine seizure and, to verify neuroprotective activity, we also evaluated the percentage of neuronal damage in the CA1 and CA3 fields of hippocampus after status epilepticus induced by pilocarpine. Swiss female mice were treated orally (gavage) and divided into groups according to the study, among them: anticonvulsant activity [6 groups (n = 10): control (distilled water); CH (25, 50 and 100 mg/kg); Phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], antioxidant activity [4 groups (n = 10): control (distilled water), CH (50 mg/kg), phenobarbital (10 mg/kg) or oxcarbazepine (60 mg/kg)], determination of the amino acid levels [3 groups (n = 8): control (distilled water), CH (50 mg/kg) and phenobarbital (10 mg/kg)] and verification of neuronal damage [3 groups (n = 4): control (distilled water), CH (50 mg/kg) or pilocarpine (400mg/kg, intraperitoneally). The results showed that CHAMBA presented a anticonvulsant effect because it increased latency of first convulsion and latency to death parameters in all models and doses used, except the dose of 25 mg/kg, that was not significant in picrotoxin model. The evaluation of the antioxidant activity showed that Chamba reduced levels of lipid peroxidation and nitrite, and increased catalase activity in hippocampus and striatum in all models used. The determination of amino acid levels showed that Chamba increased levels of inhibitory amino acids, and reduced levels of excitatory amino acids and, finally, the evaluation of the neuroprotective activity by the percentage of neuronal damage, Chamba showed a reduced neuronal damage in the CA1 and CA3 areas of the hippocampus. In conclusion, the study suggests a modulating action carried out by the standardized extract of Justicia pectoralis on seizures by altering levels of neurotransmitters, amino acids, oxidative stress and neuronal damage, which are the mechanisms involved in the pathology.
publishDate 2015
dc.date.issued.fl_str_mv 2015-01-30
dc.date.accessioned.fl_str_mv 2016-03-28T13:00:35Z
dc.date.available.fl_str_mv 2016-03-28T13:00:35Z
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dc.identifier.citation.fl_str_mv VENÂNCIO, E. T. Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação. 2015. 184 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/15739
identifier_str_mv VENÂNCIO, E. T. Avaliação do potencial anticonvulsivante do extrato padronizado de Justicia pectoralis (Chambá): estudo de neuroproteção e mecanismo de ação. 2015. 184 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
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