Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos

Detalhes bibliográficos
Autor(a) principal: Vasconcelos, Carlos Franciney Moreira
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/40992
Resumo: Parkinson's disease (PD) is a multicentric neurodegenerative disorder that affects the central nervous system and is characterized primarily by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Its etiology is not clear, but several factors have been identified as indicators of its pathophysiology, such as neuroinflammation, mitochondrial dysfunction, oxidative stress and abnormal protein aggregation. Currently the treatments for PD are restricted to symptomatic relief, mainly for motor symptoms, and are not effective in preventing the progression of the disease. In addition, current therapy based on endogenous drug dopamine replacement, whose "gold standard" is Levodopa (L-DOPA), in the treatment of PD may trigger adverse side effects. Eugenol is a phenylpropanoid that has been widely studied due to its anti-inflammatory, anti-excitotoxic and antioxidant activities. In this way, it presents itself as a promising neuroprotective agent and may provide new therapeutic intervention strategies for the treatment of PD. The aim of this study was to investigate the effects of eugenol and / or L-DOPA on neurotoxin 6-OHDA induced by neurotoxin 6-OHDA model, through neurochemical and neurobehavioral analyzes. To evaluate the neuroprotective potential of eugenol, wistar rats (250-300 g) were used, which were submitted to the PD model by intra-atrial injection of 6-OHDA (21 μg / animal) and then treated with L-DOPA (25 mg / kg) or the association between the compounds (Eug 10 mg / kg + LD 12.5 mg / kg) orally for 14 days . On the last day of treatment, the animals were submitted to specific behavioral tests (Open field, Rota-rod and Rotational test induced by apomorphine) and, after euthanasia and dissection of the cerebral areas (ipsi and contralateral striatum, Hippocampus and Prefrontal Cortex ), the neurochemical analyzes were performed (determination of MDA, nitrite / nitrate and GSH levels). Additionally, the effect of these treatments on the body mass gain was evaluated. The results showed that eugenol had a dose-dependent effect on recovery of motor damage and spontaneous exploratory activity, as well as on mass gain in animals. In addition, the most effective dose (10 mg / kg) was able to reduce nitrite / nitrate and MDA levels, in addition to recovering the endogenous levels of GSH. The association between eugenol and L-DOPA, in turn, was shown to be more effective in some neurobehavioural parameters and in body mass gain, besides promoting an increase in GSH levels in all brain areas analyzed in relation to the group treated only with L-DOPA. However, these did not differ in the levels of MDA and nitrite / nitrate, in relation to the hemiparkinsonian animals. Thus, a neuroprotective effect of eugenol against motor and neurochemical disorders associated with the 6-OHDA-induced hemiparkinsonism model was observed. Additionally, the association between eugenol and L-DOPA was promising when compared to conventional treatment, but did not differ from this in the reduction of nitrosative stress and lipid peroxidation.
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spelling Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianosEugenol protects against the progression of neurodegenerative damage in hemiparkinsonian rats6-hidroxidopaminaEugenolLevodopaParkinson's disease (PD) is a multicentric neurodegenerative disorder that affects the central nervous system and is characterized primarily by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Its etiology is not clear, but several factors have been identified as indicators of its pathophysiology, such as neuroinflammation, mitochondrial dysfunction, oxidative stress and abnormal protein aggregation. Currently the treatments for PD are restricted to symptomatic relief, mainly for motor symptoms, and are not effective in preventing the progression of the disease. In addition, current therapy based on endogenous drug dopamine replacement, whose "gold standard" is Levodopa (L-DOPA), in the treatment of PD may trigger adverse side effects. Eugenol is a phenylpropanoid that has been widely studied due to its anti-inflammatory, anti-excitotoxic and antioxidant activities. In this way, it presents itself as a promising neuroprotective agent and may provide new therapeutic intervention strategies for the treatment of PD. The aim of this study was to investigate the effects of eugenol and / or L-DOPA on neurotoxin 6-OHDA induced by neurotoxin 6-OHDA model, through neurochemical and neurobehavioral analyzes. To evaluate the neuroprotective potential of eugenol, wistar rats (250-300 g) were used, which were submitted to the PD model by intra-atrial injection of 6-OHDA (21 μg / animal) and then treated with L-DOPA (25 mg / kg) or the association between the compounds (Eug 10 mg / kg + LD 12.5 mg / kg) orally for 14 days . On the last day of treatment, the animals were submitted to specific behavioral tests (Open field, Rota-rod and Rotational test induced by apomorphine) and, after euthanasia and dissection of the cerebral areas (ipsi and contralateral striatum, Hippocampus and Prefrontal Cortex ), the neurochemical analyzes were performed (determination of MDA, nitrite / nitrate and GSH levels). Additionally, the effect of these treatments on the body mass gain was evaluated. The results showed that eugenol had a dose-dependent effect on recovery of motor damage and spontaneous exploratory activity, as well as on mass gain in animals. In addition, the most effective dose (10 mg / kg) was able to reduce nitrite / nitrate and MDA levels, in addition to recovering the endogenous levels of GSH. The association between eugenol and L-DOPA, in turn, was shown to be more effective in some neurobehavioural parameters and in body mass gain, besides promoting an increase in GSH levels in all brain areas analyzed in relation to the group treated only with L-DOPA. However, these did not differ in the levels of MDA and nitrite / nitrate, in relation to the hemiparkinsonian animals. Thus, a neuroprotective effect of eugenol against motor and neurochemical disorders associated with the 6-OHDA-induced hemiparkinsonism model was observed. Additionally, the association between eugenol and L-DOPA was promising when compared to conventional treatment, but did not differ from this in the reduction of nitrosative stress and lipid peroxidation.A doença de Parkinson (DP) é uma desordem neurodegenerativa multicêntrica que acomete o sistema nervoso central e é caracterizada principalmente pela perda de neurônios dopaminérgicos na substância negra pars compacta (SNpc). Sua etiologia não é clara, porém vários fatores têm sido apontados como indicadores da sua fisiopatologia, tais como: neuroinflamação, disfunção mitocondrial, estresse oxidativo e agregação proteica anormal. Atualmente os tratamentos para a DP restringem-se ao alívio sintomático, principalmente para os sintomas motores, não sendo eficazes em impedir a progressão da doença. Além disso, a terapia atual, baseada na reposição de dopamina endógena por fármacos, cujo “padrão ouro” é o Levodopa (L-DOPA), no tratamento da DP pode vir a desencadear efeitos colaterais adversos. O eugenol é um fenilpropanóide que vem sendo largamente estudado, devido as suas atividades anti-inflamatória, anti-excitotóxica e antioxidante. Dessa maneira, este se apresenta como um promissor agente neuroprotetor, podendo fornecer novas estratégias de intervenção terapêutica para o tratamento da DP. O objetivo deste trabalho foi, portanto, a investigação dos efeitos do eugenol e/ou L-DOPA sobre o modelo de DP induzido pela neurotoxina 6-hidroxidopamina (6-OHDA), através de análises neuroquímicas e neurocomportamentais. Para avaliação do potencial neuroprotetor do eugenol, foram utilizados ratos wistar (250-300 g) os quais foram submetidos ao modelo de DP através de injeção intraestriatal de 6-OHDA (21 μg/ animal) e, logo em seguida, tratados com o referido bioativo (0,1, 1, 10 mg / kg), L-DOPA (25 mg / kg) ou a associação entre os compostos (Eug 10 mg / kg + LD 12,5 mg / kg) por via oral durante 14 dias. No último dia de tratamento, os animais foram submetidos a ensaios comportamentais específicos (Campo aberto, Rota-rod e Teste Rotacional induzido por apomorfina) e, após eutanásia e dissecação das áreas cerebrais (Corpo estriado ipsi e contralateral, Hipocampo e Córtex Pré-frontal), foram realizadas as análises neuroquímicas (determinação dos níveis de MDA, nitrito/nitrato e GSH). Adicionalmente, foi avaliado o efeito dos referidos tratamentos sobre o ganho de massa corpórea pelos animais. Os resultados demonstraram que o eugenol apresentou um efeito dose-dependente na recuperação dos danos motores e atividade exploratória espontânea, bem como no ganho de massa pelos animais. Ademais, a dose mais efetiva (10 mg / kg) foi capaz de reduzir os níveis de nitrito/nitrato e de MDA, além de recuperar os níveis endógenos de GSH. A associação entre eugenol e L-DOPA, por sua vez, se mostrou mais eficaz em alguns parâmetros neurocomportamentais e no ganho de massa corpórea, além de promover um aumento nos níveis de GSH em todas as áreas cerebrais analisadas em relação ao grupo tratado apenas com L-DOPA. Todavia, estes não diferiram nos níveis de MDA e nitrito/nitrato, em relação aos animais hemiparkinsonianos. Assim, percebeu-se um efeito neuroprotetor do eugenol contra as desordens motoras e neuroquímicas associadas ao modelo de hemiparkinsonismo induzido por 6-OHDA. Adicionalmente, a associação entre eugenol e L-DOPA se mostrou promissora quando comparada ao tratamento convencional, porém não diferiu deste na redução do estresse nitrosativo e da peroxidação lipídica.Cunha, Rodrigo Maranguape Silva daAguiar, Lissiana Magna VasconcelosVasconcelos, Carlos Franciney Moreira2019-04-23T18:07:45Z2019-04-23T18:07:45Z2018-02-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfVASCONCELOS, C. F. M. Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos. 2018. 108 f. Dissertação (Mestrado em Biotecnologia) - Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Ceará, Sobral, 2018.http://www.repositorio.ufc.br/handle/riufc/40992porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-04-23T18:07:45Zoai:repositorio.ufc.br:riufc/40992Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:41:15.361764Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
Eugenol protects against the progression of neurodegenerative damage in hemiparkinsonian rats
title Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
spellingShingle Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
Vasconcelos, Carlos Franciney Moreira
6-hidroxidopamina
Eugenol
Levodopa
title_short Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
title_full Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
title_fullStr Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
title_full_unstemmed Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
title_sort Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos
author Vasconcelos, Carlos Franciney Moreira
author_facet Vasconcelos, Carlos Franciney Moreira
author_role author
dc.contributor.none.fl_str_mv Cunha, Rodrigo Maranguape Silva da
Aguiar, Lissiana Magna Vasconcelos
dc.contributor.author.fl_str_mv Vasconcelos, Carlos Franciney Moreira
dc.subject.por.fl_str_mv 6-hidroxidopamina
Eugenol
Levodopa
topic 6-hidroxidopamina
Eugenol
Levodopa
description Parkinson's disease (PD) is a multicentric neurodegenerative disorder that affects the central nervous system and is characterized primarily by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Its etiology is not clear, but several factors have been identified as indicators of its pathophysiology, such as neuroinflammation, mitochondrial dysfunction, oxidative stress and abnormal protein aggregation. Currently the treatments for PD are restricted to symptomatic relief, mainly for motor symptoms, and are not effective in preventing the progression of the disease. In addition, current therapy based on endogenous drug dopamine replacement, whose "gold standard" is Levodopa (L-DOPA), in the treatment of PD may trigger adverse side effects. Eugenol is a phenylpropanoid that has been widely studied due to its anti-inflammatory, anti-excitotoxic and antioxidant activities. In this way, it presents itself as a promising neuroprotective agent and may provide new therapeutic intervention strategies for the treatment of PD. The aim of this study was to investigate the effects of eugenol and / or L-DOPA on neurotoxin 6-OHDA induced by neurotoxin 6-OHDA model, through neurochemical and neurobehavioral analyzes. To evaluate the neuroprotective potential of eugenol, wistar rats (250-300 g) were used, which were submitted to the PD model by intra-atrial injection of 6-OHDA (21 μg / animal) and then treated with L-DOPA (25 mg / kg) or the association between the compounds (Eug 10 mg / kg + LD 12.5 mg / kg) orally for 14 days . On the last day of treatment, the animals were submitted to specific behavioral tests (Open field, Rota-rod and Rotational test induced by apomorphine) and, after euthanasia and dissection of the cerebral areas (ipsi and contralateral striatum, Hippocampus and Prefrontal Cortex ), the neurochemical analyzes were performed (determination of MDA, nitrite / nitrate and GSH levels). Additionally, the effect of these treatments on the body mass gain was evaluated. The results showed that eugenol had a dose-dependent effect on recovery of motor damage and spontaneous exploratory activity, as well as on mass gain in animals. In addition, the most effective dose (10 mg / kg) was able to reduce nitrite / nitrate and MDA levels, in addition to recovering the endogenous levels of GSH. The association between eugenol and L-DOPA, in turn, was shown to be more effective in some neurobehavioural parameters and in body mass gain, besides promoting an increase in GSH levels in all brain areas analyzed in relation to the group treated only with L-DOPA. However, these did not differ in the levels of MDA and nitrite / nitrate, in relation to the hemiparkinsonian animals. Thus, a neuroprotective effect of eugenol against motor and neurochemical disorders associated with the 6-OHDA-induced hemiparkinsonism model was observed. Additionally, the association between eugenol and L-DOPA was promising when compared to conventional treatment, but did not differ from this in the reduction of nitrosative stress and lipid peroxidation.
publishDate 2018
dc.date.none.fl_str_mv 2018-02-06
2019-04-23T18:07:45Z
2019-04-23T18:07:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv VASCONCELOS, C. F. M. Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos. 2018. 108 f. Dissertação (Mestrado em Biotecnologia) - Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Ceará, Sobral, 2018.
http://www.repositorio.ufc.br/handle/riufc/40992
identifier_str_mv VASCONCELOS, C. F. M. Eugenol protege contra a progressão dos danos neurodegenerativos em ratos hemiparkinsonianos. 2018. 108 f. Dissertação (Mestrado em Biotecnologia) - Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Ceará, Sobral, 2018.
url http://www.repositorio.ufc.br/handle/riufc/40992
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dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
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reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
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