NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/549 |
Resumo: | The statins are drugs used to treat hypercholesterolemia because their mechanism of action is to inhibit the enzyme HMG CoA reductase what is part of cholesterol biosynthesis. Studies have shown that statins have pleiotropic effects and action in the central nervous system (CNS) simvastatin (SIN) is evaluated as a prevention strategy in the treatment of neurodegenerative diseases such as Alzheimers and Parkinson’s. SIN is metabolized rapidly in the body with nonspecifically delivery to tissues. An alternative solution to these problems is to use nanocarriers that take the drugs to their target site. The nanocapsules systems are considered vectors for the administration of lipophilic substances by having a large surface area. The objective is to evaluate the effect of simvastatin nanocoated memory and type behavior anxious rats. The suspensions of simvastatin nanocapsules (NS) were produced by the interfacial deposition technique preformed polymer described by Fessi et al (1989) adapted by Venturini et al (2011). NS were characterized by dynamic light scattering (Zetasizer), Zeta potential, pH determination, drug content and encapsulation efficiency. The rats Wistar adult young (3 months, 250g-300g), midle aged (8 months, 450-500g) and adult old (12 to 13 months, 500g-700g) were from the central University vivarium Federal de Santa Maria and all procedures were performed after approval of CEUA (nº002/ 2016 protocol). First it performed a chronic treatment at the dose of 15 mg/kg or 30 mg/kg and SIN or NS rats young adults orally (v.o.) for 21 days and 30 min before testing of the inhibitory avoidance task (EI) was administered scopolamine amnesia-inducing (ESC) at a dose of 0.4 mg/kg. After this protocol was performed an acute treatment in young-adult rats with SIN or NS at a dose of 15mg/kg and 30 min before the EI test was administered i.p ESC or 75 min the other amnesic inducer ketamine (CET). The third protocol rats middle age was performed an acute treatment with SIN or NS v.o. at a dose of 15 mg/kg and the animals were evaluated for aversive memory in EI. In the last protocol adults age animal were treated chronically v.o. with SIN or NS at a dose of 15 mg/kg were evaluated in open field task, Plus Maze and EI. The results show that NS presented the particle diameter of 226.9 ± 16.4 nm, polydispersity 0.165 ± 0.04, zeta potential (mV) -8.4 ± 1.07) 6.67 ± 0.27 pH, efficiency encapsulation 77.7% and content of 85%. These parameters are in accordance with the methodology. Chronic treatment with SIN could reverse the damage caused by the ESC in memory at both doses compared to the SAL group. Acute doses of NS reverse the damage 11 caused in the memory of both the ESC and CET as compared to SAL groups. The SIN has a tendency effect not as expressive as the NS. In the acute treatment dose with NS or SIN adult-aged rats NS could be effective in reversing the natural memory loss. Since SIN had no effect. Chronic treatment with NS and SIN adults-old rats could reverse the natural loss of memory in the test of EI. There was no significant difference in locomotor and exploratory activity of animals. The adult aged treated with NS for a longer time in the open arms in elevated cross maze and the number of dips was greater than salt and SIN, indicating an anxiolytic effect of NS. We conclude that the NS has a more significant effect on acute doses and an anxiolytic effect on chronic treatment in adults-old mice. |
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Boeck, Carina RodriguesBarros, Daniela MartíSantos, Cláudia Lange dosGuerino, Bruna Costabeber2018-08-17T11:40:09Z2016-07-12Guerino, Bruna Costabeber. NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS. 2016. 85f. Dissertação( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/549The statins are drugs used to treat hypercholesterolemia because their mechanism of action is to inhibit the enzyme HMG CoA reductase what is part of cholesterol biosynthesis. Studies have shown that statins have pleiotropic effects and action in the central nervous system (CNS) simvastatin (SIN) is evaluated as a prevention strategy in the treatment of neurodegenerative diseases such as Alzheimers and Parkinson’s. SIN is metabolized rapidly in the body with nonspecifically delivery to tissues. An alternative solution to these problems is to use nanocarriers that take the drugs to their target site. The nanocapsules systems are considered vectors for the administration of lipophilic substances by having a large surface area. The objective is to evaluate the effect of simvastatin nanocoated memory and type behavior anxious rats. The suspensions of simvastatin nanocapsules (NS) were produced by the interfacial deposition technique preformed polymer described by Fessi et al (1989) adapted by Venturini et al (2011). NS were characterized by dynamic light scattering (Zetasizer), Zeta potential, pH determination, drug content and encapsulation efficiency. The rats Wistar adult young (3 months, 250g-300g), midle aged (8 months, 450-500g) and adult old (12 to 13 months, 500g-700g) were from the central University vivarium Federal de Santa Maria and all procedures were performed after approval of CEUA (nº002/ 2016 protocol). First it performed a chronic treatment at the dose of 15 mg/kg or 30 mg/kg and SIN or NS rats young adults orally (v.o.) for 21 days and 30 min before testing of the inhibitory avoidance task (EI) was administered scopolamine amnesia-inducing (ESC) at a dose of 0.4 mg/kg. After this protocol was performed an acute treatment in young-adult rats with SIN or NS at a dose of 15mg/kg and 30 min before the EI test was administered i.p ESC or 75 min the other amnesic inducer ketamine (CET). The third protocol rats middle age was performed an acute treatment with SIN or NS v.o. at a dose of 15 mg/kg and the animals were evaluated for aversive memory in EI. In the last protocol adults age animal were treated chronically v.o. with SIN or NS at a dose of 15 mg/kg were evaluated in open field task, Plus Maze and EI. The results show that NS presented the particle diameter of 226.9 ± 16.4 nm, polydispersity 0.165 ± 0.04, zeta potential (mV) -8.4 ± 1.07) 6.67 ± 0.27 pH, efficiency encapsulation 77.7% and content of 85%. These parameters are in accordance with the methodology. Chronic treatment with SIN could reverse the damage caused by the ESC in memory at both doses compared to the SAL group. Acute doses of NS reverse the damage 11 caused in the memory of both the ESC and CET as compared to SAL groups. The SIN has a tendency effect not as expressive as the NS. In the acute treatment dose with NS or SIN adult-aged rats NS could be effective in reversing the natural memory loss. Since SIN had no effect. Chronic treatment with NS and SIN adults-old rats could reverse the natural loss of memory in the test of EI. There was no significant difference in locomotor and exploratory activity of animals. The adult aged treated with NS for a longer time in the open arms in elevated cross maze and the number of dips was greater than salt and SIN, indicating an anxiolytic effect of NS. We conclude that the NS has a more significant effect on acute doses and an anxiolytic effect on chronic treatment in adults-old mice.As estatinas são fármacos utilizados no tratamento da hipercolesterolemia pois seu mecanismo de ação é diminuir a síntese da enzima HMG COA-redutase que faz parte da biossíntese do colesterol. Estudos têm mostrado que as estatinas possuem efeitos pleiotrópicos como ação no sistema nervoso central (SNC) A sinvastatina (SIN) está sendo estuda como uma estratégia de prevenção no tratamento de doenças neurodegenerativas como Alzheimer e Parkinson. Um dos problemas da SIN é que ela é rapidamente metabolizada no organismo e entregue de forma inespecífica aos tecidos. Uma alternativa para solução destes problemas é utilizar nanocarreadores que levam os fármacos ao seu sítio alvo. As nanocápsulas são sistemas considerados vetores para a administração de substâncias lipofílicas por possuírem uma grande área superficial. O objetivo do trabalho foi avaliar o efeito da sinvastatina nanoencapsulada na memória e no comportamento do tipo ansioso em ratos. As suspensões de nanocápsulas de sinvastatina (NS) foram produzidas através da técnica de deposição interfacial do polímero pré-formado descrita por Fessi e colaboradores (1989) e adaptada por Venturini e colaboradores (2011). As NS foram caracterizadas através do espalhamento de luz dinâmico (Zetasizer), potencial Zeta, determinação do pH, teor de fármaco e eficiência de encapsulação. Não foi realizado tratamento com nanocápsulas branca (NB), pois em trabalho anterior do grupo de pesquisa (ALVES, 2015), não foi observada diferença significativa entre os grupos SAL, NB e Näive. Os animais ratos Wistar adultos-jovens (3 meses, 250g-300g), ratos adultos meia idade (8 meses, 450-500g) e ratos adultos-velhos (12 a 13 meses, 500g-700g) foram provenientes do biotério central da Universidade Federal de Santa Maria e todos os procedimentos foram realizados após aprovação do Conselho de Ética do uso de animais do Centro Universitário Franciscano (CEUA) (protocolo nº002/2016). Primeiramente foi realizado um tratamento crônico na dose de 15 mg/kg ou 30 mg/kg com SIN ou NS em ratos adultos-jovens via oral (v.o.) durante 21 dias e 30 min antes do teste da tarefa da Esquiva Inibitória (EI) foi administrado o indutor amnésico escopolamina (ESC) na dose de 0,4 mg/kg. Após este protocolo foi realizado um tratamento agudo em ratos adultos-jovens com SIN ou NS na dose de 15mg/kg (v.o) e 30 min antes do teste de EI foi administrado i.p ESC e 75min o outro indutor amnésico a cetamina (CET). O terceiro protocolo foi realizado um tratamento agudo 9 com SIN ou NS v.o. na dose de 15 mg/kg e os animais foram avaliados quanto a memória aversiva na EI. No último protocolo os animais adultos-velhos foram tratados cronicamente v.o. com SIN ou NS na dose de 15 mg/kg e foram avaliados nos testes de Campo Aberto, Labirinto da Cruz Elevado e EI. As NS apresentaram o diâmetro de partícula 226,9 ± 16,4 nm, índice de polidispersão 0,165 ± 0,04, potencial zeta (mV) -8,4 ± 1,07), pH 6,67 ± 0,27, eficiência de encapsulação 77,7% e teor 85%. Estes parâmetros estão de acordo com a metodologia utilizada. O tratamento crônico com a SIN conseguiu reverter o dano na memória provocado pela ESC em ambas as doses comparado ao grupo SAL. As doses agudas de NS conseguirem o reverter o dano causado na memória tanto da ESC e CET. A SIN tem uma tendência efeito não tão expressivo quanto a NS. No tratamento de dose aguda com NS ou SIN em ratos adultos-meia idade a NS conseguiu ter efeito na reversão da perda natural da memória. Já a SIN não teve efeito. O tratamento crônico com NS e SIN nos ratos adultos-velhos conseguiu reverter a perda natural da memória no teste da EI. Não houve diferença significativa na locomoção e na atividade exploratória dos animais. Os animais tratados com NS ficaram durante mais tempo nos braços abertos no Labirinto de Cruz elevado e o número de mergulhos foi maior que o SAL e SIN indicando um efeito ansiolítico. Conclui-se que a NS possui um efeito mais expressivo em doses agudas e um efeito ansiolítico no tratamento crônico em ratos adultos-velhos.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-17T11:40:09Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_BrunaCostabeberGuerino.pdf: 1767438 bytes, checksum: 21a9128d4c5ddfc4768c4fa4fdc8325c (MD5)Made available in DSpace on 2018-08-17T11:40:09Z (GMT). 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dc.title.por.fl_str_mv |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
title |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
spellingShingle |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS Guerino, Bruna Costabeber Estatinas; Cognição; Nanopartículas; Neuroproteção. Cognition; nanoparticles; neuroprotection; statins Biociências e Nanomateriais |
title_short |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
title_full |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
title_fullStr |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
title_full_unstemmed |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
title_sort |
NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS |
author |
Guerino, Bruna Costabeber |
author_facet |
Guerino, Bruna Costabeber |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Boeck, Carina Rodrigues |
dc.contributor.referee1.fl_str_mv |
Barros, Daniela Martí |
dc.contributor.referee2.fl_str_mv |
Santos, Cláudia Lange dos |
dc.contributor.author.fl_str_mv |
Guerino, Bruna Costabeber |
contributor_str_mv |
Boeck, Carina Rodrigues Barros, Daniela Martí Santos, Cláudia Lange dos |
dc.subject.por.fl_str_mv |
Estatinas; Cognição; Nanopartículas; Neuroproteção. |
topic |
Estatinas; Cognição; Nanopartículas; Neuroproteção. Cognition; nanoparticles; neuroprotection; statins Biociências e Nanomateriais |
dc.subject.eng.fl_str_mv |
Cognition; nanoparticles; neuroprotection; statins |
dc.subject.cnpq.fl_str_mv |
Biociências e Nanomateriais |
description |
The statins are drugs used to treat hypercholesterolemia because their mechanism of action is to inhibit the enzyme HMG CoA reductase what is part of cholesterol biosynthesis. Studies have shown that statins have pleiotropic effects and action in the central nervous system (CNS) simvastatin (SIN) is evaluated as a prevention strategy in the treatment of neurodegenerative diseases such as Alzheimers and Parkinson’s. SIN is metabolized rapidly in the body with nonspecifically delivery to tissues. An alternative solution to these problems is to use nanocarriers that take the drugs to their target site. The nanocapsules systems are considered vectors for the administration of lipophilic substances by having a large surface area. The objective is to evaluate the effect of simvastatin nanocoated memory and type behavior anxious rats. The suspensions of simvastatin nanocapsules (NS) were produced by the interfacial deposition technique preformed polymer described by Fessi et al (1989) adapted by Venturini et al (2011). NS were characterized by dynamic light scattering (Zetasizer), Zeta potential, pH determination, drug content and encapsulation efficiency. The rats Wistar adult young (3 months, 250g-300g), midle aged (8 months, 450-500g) and adult old (12 to 13 months, 500g-700g) were from the central University vivarium Federal de Santa Maria and all procedures were performed after approval of CEUA (nº002/ 2016 protocol). First it performed a chronic treatment at the dose of 15 mg/kg or 30 mg/kg and SIN or NS rats young adults orally (v.o.) for 21 days and 30 min before testing of the inhibitory avoidance task (EI) was administered scopolamine amnesia-inducing (ESC) at a dose of 0.4 mg/kg. After this protocol was performed an acute treatment in young-adult rats with SIN or NS at a dose of 15mg/kg and 30 min before the EI test was administered i.p ESC or 75 min the other amnesic inducer ketamine (CET). The third protocol rats middle age was performed an acute treatment with SIN or NS v.o. at a dose of 15 mg/kg and the animals were evaluated for aversive memory in EI. In the last protocol adults age animal were treated chronically v.o. with SIN or NS at a dose of 15 mg/kg were evaluated in open field task, Plus Maze and EI. The results show that NS presented the particle diameter of 226.9 ± 16.4 nm, polydispersity 0.165 ± 0.04, zeta potential (mV) -8.4 ± 1.07) 6.67 ± 0.27 pH, efficiency encapsulation 77.7% and content of 85%. These parameters are in accordance with the methodology. Chronic treatment with SIN could reverse the damage caused by the ESC in memory at both doses compared to the SAL group. Acute doses of NS reverse the damage 11 caused in the memory of both the ESC and CET as compared to SAL groups. The SIN has a tendency effect not as expressive as the NS. In the acute treatment dose with NS or SIN adult-aged rats NS could be effective in reversing the natural memory loss. Since SIN had no effect. Chronic treatment with NS and SIN adults-old rats could reverse the natural loss of memory in the test of EI. There was no significant difference in locomotor and exploratory activity of animals. The adult aged treated with NS for a longer time in the open arms in elevated cross maze and the number of dips was greater than salt and SIN, indicating an anxiolytic effect of NS. We conclude that the NS has a more significant effect on acute doses and an anxiolytic effect on chronic treatment in adults-old mice. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-07-12 |
dc.date.accessioned.fl_str_mv |
2018-08-17T11:40:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Guerino, Bruna Costabeber. NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS. 2016. 85f. Dissertação( 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/549 |
identifier_str_mv |
Guerino, Bruna Costabeber. NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS. 2016. 85f. Dissertação( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS . |
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http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/549 |
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por |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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Programa de Pós-Graduação em Nanociências |
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UNIFRA |
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Brasil |
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Biociências e Nanomateriais |
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Centro Universitário Franciscano |
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