AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS

Detalhes bibliográficos
Autor(a) principal: Ferreira, Carla Fontoura
Data de Publicação: 2017
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional Universidade Franciscana
Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/575
Resumo: Reactive species (ERs) and oxidative stress contribute to the pathophysiology of several diseases including dementia. An innovative alternative for protecting organs such as the brain is the use of antioxidant-like flavonoids such as naringin and naringenin. However, these two compounds have low bioavailability when administered orally. An alternative to overcome this limitation is the use of nanocarriers, such as nanocapsules (NC). Therefore, the present study aimed to evaluate the neuroprotective effect of naringin and naringenin in a model of streptozotocin (STZ) -induced dementia in mice. The profile of drug release from in vitro suspensions was evaluated as well as the effects of nanoencapsulated drugs on cell viability with Vero cell line. In addition, the involvement of oxidative stress in the brain tissue of mice was verified. Naringin and naringenin NC had acid pH, particle diameter less than 95 nm, polydispersity index (IPD) of less than 0.2. The zeta potential was negative, between -12.46 and -17.6 mV, and the encapsulation efficiency was 93% for naringin and 95% for naringenin. For the study of the release profile, the dialysis technique was used, with 46.5% of naringin and 6.9% of naringenin being released in the medium, in a period of 9h. The results of the cell viability assay showed that the NC suspensions caused a reduction in cell viability of Vero cells at concentrations of 5, 50 and 500 μg / ml when compared to the control at the 24 and 72h incubation periods. For in vivo evaluation of neuroprotection the mice were pretreated for 15 days by oral (vo) with the suspension of white nanocapsules (NB), NC containing the mixture naringin and naringenin (N-NANG), suspension of naringin and naringenin in the form Free (NANG) and vehicle (Sham) at dose 10 mg / kg body weight. Subsequently, stereotactic surgery was performed for intracerebroventricular (i.c.v) infusion of STZ or FAC (cerebral artificial fluid). Behavioral tasks were then initiated. In the open field task the locomotor activity differed in the test section in the NB + STZ group evidenced by a hyperlocomotion between the mice of this experimental group. For exploratory activity there was no significant difference between groups. In the evaluation of the short-term memory in the task of object recognition the animals treated with N-NANG did not recognize the new object. For the long-term memory there was learning only for the mice treated with NB. The mice treated with NB + STZ had memory impairment assessed in the task of inhibitory avoidance, and pre-treatment with N-NANG prevented this effect. In the evaluation of the anti-depressive and anxiolytic-type effects, it was observed that the NNANG + STZ induced greater body activity in the twist parameter in the tail suspension task and in the high "zero" labyrinth there was an increase in the number of spies Relative to the free drug. Regarding the levels of brain antioxidants, there were no changes in the levels of reduced glutathione (GSH) and catalase activity (CAT). The NB + STZ group significantly increased levels of brain lipid peroxidation of thiobarbituric acid reactive species (TBA). N-NANG administration reduced the peroxidation induced by STZ. Thus, it can be concluded that the CNs present characteristics suitable for oral administration. In vivo studies demonstrate that pre-treatment with naringin and naringenin NC was preventative and able to reverse memory deficits, type-depressive and anxiolytic behavior caused by STZ in mice. However, this preventive effect was not observed with the flavonoids in the free form.
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spelling Boeck, Carina RodriguesRaffin , Renata PlatcheckSilva, Rosane Souza daVinade, Lucia Helena do CantoRossato, JussaneViezzer, ChristianFerreira, Carla Fontoura2018-08-20T12:34:53Z2017-03-30Ferreira, Carla Fontoura. AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS. 2017. 132f. Tese( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/575Reactive species (ERs) and oxidative stress contribute to the pathophysiology of several diseases including dementia. An innovative alternative for protecting organs such as the brain is the use of antioxidant-like flavonoids such as naringin and naringenin. However, these two compounds have low bioavailability when administered orally. An alternative to overcome this limitation is the use of nanocarriers, such as nanocapsules (NC). Therefore, the present study aimed to evaluate the neuroprotective effect of naringin and naringenin in a model of streptozotocin (STZ) -induced dementia in mice. The profile of drug release from in vitro suspensions was evaluated as well as the effects of nanoencapsulated drugs on cell viability with Vero cell line. In addition, the involvement of oxidative stress in the brain tissue of mice was verified. Naringin and naringenin NC had acid pH, particle diameter less than 95 nm, polydispersity index (IPD) of less than 0.2. The zeta potential was negative, between -12.46 and -17.6 mV, and the encapsulation efficiency was 93% for naringin and 95% for naringenin. For the study of the release profile, the dialysis technique was used, with 46.5% of naringin and 6.9% of naringenin being released in the medium, in a period of 9h. The results of the cell viability assay showed that the NC suspensions caused a reduction in cell viability of Vero cells at concentrations of 5, 50 and 500 μg / ml when compared to the control at the 24 and 72h incubation periods. For in vivo evaluation of neuroprotection the mice were pretreated for 15 days by oral (vo) with the suspension of white nanocapsules (NB), NC containing the mixture naringin and naringenin (N-NANG), suspension of naringin and naringenin in the form Free (NANG) and vehicle (Sham) at dose 10 mg / kg body weight. Subsequently, stereotactic surgery was performed for intracerebroventricular (i.c.v) infusion of STZ or FAC (cerebral artificial fluid). Behavioral tasks were then initiated. In the open field task the locomotor activity differed in the test section in the NB + STZ group evidenced by a hyperlocomotion between the mice of this experimental group. For exploratory activity there was no significant difference between groups. In the evaluation of the short-term memory in the task of object recognition the animals treated with N-NANG did not recognize the new object. For the long-term memory there was learning only for the mice treated with NB. The mice treated with NB + STZ had memory impairment assessed in the task of inhibitory avoidance, and pre-treatment with N-NANG prevented this effect. In the evaluation of the anti-depressive and anxiolytic-type effects, it was observed that the NNANG + STZ induced greater body activity in the twist parameter in the tail suspension task and in the high "zero" labyrinth there was an increase in the number of spies Relative to the free drug. Regarding the levels of brain antioxidants, there were no changes in the levels of reduced glutathione (GSH) and catalase activity (CAT). The NB + STZ group significantly increased levels of brain lipid peroxidation of thiobarbituric acid reactive species (TBA). N-NANG administration reduced the peroxidation induced by STZ. Thus, it can be concluded that the CNs present characteristics suitable for oral administration. In vivo studies demonstrate that pre-treatment with naringin and naringenin NC was preventative and able to reverse memory deficits, type-depressive and anxiolytic behavior caused by STZ in mice. However, this preventive effect was not observed with the flavonoids in the free form.As espécies reativas (ERs) e o estresse oxidativo contribuem para a fisiopatologia de diversas doenças entre elas a demência. Uma alternativa inovadora de proteção aos órgãos como o cérebro é o uso de flavonoides com ação antioxidante como a naringina e naringenina. No entanto, esses dois compostos apresentam baixa biodisponibilidade quando administrados pela via oral. Uma alternativa para contornar esta limitação é o uso de nanocarreadores, como as nanocápsulas (NC). Diante disso, o presente estudo teve por objetivo avaliar o efeito neuroprotetor de NC contendo naringina e naringenina em modelo de demência induzida por estreptozotocina (STZ) em camundongos. Foram avaliados o perfil de liberação dos fármacos a partir das suspensões in vitro assim como determinados os efeitos dos fármacos nanoencapsulados na viabilidade celular com linhagem de células Vero. Além disso, foi verificado o envolvimento do estresse oxidativo no tecido cerebral dos camundongos. As NC de naringina e naringenina apresentaram pH ácido, diâmetro de partícula inferior a 95 nm, índice de polidispersão (IPD) menor que 0,2. O potencial zeta foi negativo, entre -12,46 e -17,6 mV e a eficiência de encapsulação foi de 93% para naringina e 95% para a naringenina. Para o estudo do perfil de liberação, foi empregada a técnica de diálise, sendo que 46,5% da naringina e 6,9% da naringenina foram liberadas no meio, em um período de 9h. Os resultados do ensaio de viabilidade celular mostraram que as suspensões de NC causaram redução da viabilidade celular das células Vero nas concentrações de 5, 50 e 500 μg/mL quando comparadas ao controle nos períodos de 24 e 72h de incubação. Para avaliação in vivo da neuroproteção os camundongos foram pré-tratados durante 15 dias via oral (v.o) com a suspensão de nanocápsulas brancas (NB), NC contendo a mistura naringina e naringenina (N-NANG), suspensão de naringina e naringenina na forma livre (NANG) e veículo (Sham) na dose 10 mg/kg corporal. Subsequentemente foi realizada a cirurgia estereotáxica para a infusão via intracerebroventricular (i.c.v) de STZ ou FAC (fluido artificial cerebral). Posteriormente foram iniciadas as tarefas comportamentais. Na tarefa do campo aberto a atividade locomotora diferiu na seção teste no grupo NB+STZ evidenciada por uma hiperlocomoção entre os camundongos deste grupo experimental. Para atividade exploratória não houve diferença significativa entre os grupos. Na avaliação da memória de curto prazo na tarefa de reconhecimento de objetos os animais tratados com N-NANG não reconheceram o objeto novo. Para a memória de longo prazo houve aprendizagem somente para os camundongos tratados com NB. Os camundongos tratados com NB+STZ tiveram prejuízo de memória avaliado na tarefa da esquiva inibitória, e o pré-tratamento com N-NANG preveniu esse efeito. Na avaliação do efeito tipo anti-depressivo e tipo-ansiolítico observa-se que as N-NANG+STZ induziram maior atividade corporal no parâmetro torções na tarefa da suspensão da cauda e no labirinto em “zero” elevado houve um aumento do número de espiadas em relação ao fármaco livre. Com relação aos níveis de antioxidantes cerebrais não houve alterações nos níveis de Glutationa reduzida (GSH) e na atividade da catalase (CAT). O grupo NB+STZ aumentou significativamente os níveis de peroxidação lipídica cerebral de espécies reativas ao ácido tiobarbitúrico (TBA). Já administração de N-NANG reduziu a peroxidação induzida pela STZ. Com isso pode-se concluir que as NC apresentam características adequadas para administração via oral. Os estudos in vivo demonstram que o pré- tratamento com as NC de naringina e naringenina foi preventivo e capaz de reverter os déficits de memória, comportamento tipo-depressivo e ansiolítico causado pela STZ nos camundongos. Contudo, esse efeito preventivo não foi observado com os flavonoides na forma livre.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-20T12:34:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CarlaFontouraFerrreira.pdf: 19008440 bytes, checksum: b5b118a8e2abb810388a00dc8e27ac80 (MD5)Made available in DSpace on 2018-08-20T12:34:53Z (GMT). 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dc.title.por.fl_str_mv AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
title AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
spellingShingle AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
Ferreira, Carla Fontoura
Nanopartículas; Demência; Naringina; Naringenina
Nanoparticles; Dementia; Naringin; Naringenin
Biociências e Nanomateriais
title_short AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
title_full AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
title_fullStr AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
title_full_unstemmed AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
title_sort AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS
author Ferreira, Carla Fontoura
author_facet Ferreira, Carla Fontoura
author_role author
dc.contributor.advisor1.fl_str_mv Boeck, Carina Rodrigues
dc.contributor.advisor-co1.fl_str_mv Raffin , Renata Platcheck
dc.contributor.referee1.fl_str_mv Silva, Rosane Souza da
dc.contributor.referee2.fl_str_mv Vinade, Lucia Helena do Canto
dc.contributor.referee3.fl_str_mv Rossato, Jussane
dc.contributor.referee4.fl_str_mv Viezzer, Christian
dc.contributor.author.fl_str_mv Ferreira, Carla Fontoura
contributor_str_mv Boeck, Carina Rodrigues
Raffin , Renata Platcheck
Silva, Rosane Souza da
Vinade, Lucia Helena do Canto
Rossato, Jussane
Viezzer, Christian
dc.subject.por.fl_str_mv Nanopartículas; Demência; Naringina; Naringenina
topic Nanopartículas; Demência; Naringina; Naringenina
Nanoparticles; Dementia; Naringin; Naringenin
Biociências e Nanomateriais
dc.subject.eng.fl_str_mv Nanoparticles; Dementia; Naringin; Naringenin
dc.subject.cnpq.fl_str_mv Biociências e Nanomateriais
description Reactive species (ERs) and oxidative stress contribute to the pathophysiology of several diseases including dementia. An innovative alternative for protecting organs such as the brain is the use of antioxidant-like flavonoids such as naringin and naringenin. However, these two compounds have low bioavailability when administered orally. An alternative to overcome this limitation is the use of nanocarriers, such as nanocapsules (NC). Therefore, the present study aimed to evaluate the neuroprotective effect of naringin and naringenin in a model of streptozotocin (STZ) -induced dementia in mice. The profile of drug release from in vitro suspensions was evaluated as well as the effects of nanoencapsulated drugs on cell viability with Vero cell line. In addition, the involvement of oxidative stress in the brain tissue of mice was verified. Naringin and naringenin NC had acid pH, particle diameter less than 95 nm, polydispersity index (IPD) of less than 0.2. The zeta potential was negative, between -12.46 and -17.6 mV, and the encapsulation efficiency was 93% for naringin and 95% for naringenin. For the study of the release profile, the dialysis technique was used, with 46.5% of naringin and 6.9% of naringenin being released in the medium, in a period of 9h. The results of the cell viability assay showed that the NC suspensions caused a reduction in cell viability of Vero cells at concentrations of 5, 50 and 500 μg / ml when compared to the control at the 24 and 72h incubation periods. For in vivo evaluation of neuroprotection the mice were pretreated for 15 days by oral (vo) with the suspension of white nanocapsules (NB), NC containing the mixture naringin and naringenin (N-NANG), suspension of naringin and naringenin in the form Free (NANG) and vehicle (Sham) at dose 10 mg / kg body weight. Subsequently, stereotactic surgery was performed for intracerebroventricular (i.c.v) infusion of STZ or FAC (cerebral artificial fluid). Behavioral tasks were then initiated. In the open field task the locomotor activity differed in the test section in the NB + STZ group evidenced by a hyperlocomotion between the mice of this experimental group. For exploratory activity there was no significant difference between groups. In the evaluation of the short-term memory in the task of object recognition the animals treated with N-NANG did not recognize the new object. For the long-term memory there was learning only for the mice treated with NB. The mice treated with NB + STZ had memory impairment assessed in the task of inhibitory avoidance, and pre-treatment with N-NANG prevented this effect. In the evaluation of the anti-depressive and anxiolytic-type effects, it was observed that the NNANG + STZ induced greater body activity in the twist parameter in the tail suspension task and in the high "zero" labyrinth there was an increase in the number of spies Relative to the free drug. Regarding the levels of brain antioxidants, there were no changes in the levels of reduced glutathione (GSH) and catalase activity (CAT). The NB + STZ group significantly increased levels of brain lipid peroxidation of thiobarbituric acid reactive species (TBA). N-NANG administration reduced the peroxidation induced by STZ. Thus, it can be concluded that the CNs present characteristics suitable for oral administration. In vivo studies demonstrate that pre-treatment with naringin and naringenin NC was preventative and able to reverse memory deficits, type-depressive and anxiolytic behavior caused by STZ in mice. However, this preventive effect was not observed with the flavonoids in the free form.
publishDate 2017
dc.date.issued.fl_str_mv 2017-03-30
dc.date.accessioned.fl_str_mv 2018-08-20T12:34:53Z
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dc.identifier.citation.fl_str_mv Ferreira, Carla Fontoura. AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS. 2017. 132f. Tese( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .
dc.identifier.uri.fl_str_mv http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/575
identifier_str_mv Ferreira, Carla Fontoura. AVALIAÇÃO DO EFEITO NEUROPROTETOR DA NARINGINA E NARINGENINA NANOENCAPSULADAS EM MODELO DE DEMÊNCIA INDUZIDA POR ESTREPTOZOTOCINA EM CAMUNDONGOS. 2017. 132f. Tese( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .
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