EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Universidade Franciscana |
Texto Completo: | http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/206 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/291 |
Resumo: | Creatine is a biomolecule endogenously synthesized from amino acids which can also be obtained through the diet. But it does not permeate easily through the blood-brain barrier (BBB), so the brain must supply their needs through the synthesis of creatine in the central nervous system (CNS) by itself. Creatine has a major role in maintaining stable levels of adenosine triphosphate (ATP) thus keeping the whole body in a proper condition. Neurodegenerative diseases leads to decreases in ATP levels, which compromises cellular metabolism, generating the increase of reactive species that could lead to neuronal cell death. Therefore, it becomes important to increase creatine levels in neurodegenerative diseases, so it could provide new alternative treatments for these diseases. This study aimed to develop and characterize liposomes with creatine, as well as investigate its protective effect in ischemia and reperfusion (I/R) brain model. Two methodologies were used for the preparation of liposomes, the lipid film hydration and ethanol injection. Due the best results were obtained by the ethanol injection method, this was chosen for the preparation of liposomes in in vivo tests. The rats were tested using I/R by clamping bilateral carotid arteries and different groups were treated with creatine (30 mg/kg) in free form (Liv+I/R) and liposomed (Lip+I/R) and compared with the control group and I/R. The animals motor activity, exploratory and memory abilities were evaluated through field tests and passive avoidance, 24 and 48 hours after I/R, respectively. After 72 hours, the animals were euthanized and the brains removed for biochemical determination of levels of reactive species and ascorbic acid (AA), and the biochemical breakdown activity of superoxide dismutase (SOD) and catalase (CAT). The suspensions of liposomes used for the in vivo treatment had homogenous average particle diameter (154 ± 6.9 nm), low polydispersity index (0.211 ± 0.019), pH near neutral (around 6.7), negative potential Zeta (-21 ± 1.8 mV) and association rate around 31%. The results of field tests have shown that I/R caused a change in exploratory activity of animals and increased oxidative stress in the brain of rats subjected to I/R. Liposomes creatine protected the change in exploratory activity and increased oxidative stress in rat cortex. Already in free form, creatine was not able to protect against these changes. With these results, we can conclude that the production of liposomes containing creatine technological feasibility presented, demonstrating the potential to increase the bioavailability of creatine into the CNS via the BBB. |
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Alves, Marta PalmaCPF:47427582004Luchese, CristianeCPF:00490362036CPF:01459841093http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4217888H4Borin, Diego Becker2018-06-27T18:56:03Z2013-03-26BORIN, Diego Becker. EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA. 2013. 72 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2013.http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/206http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/291Creatine is a biomolecule endogenously synthesized from amino acids which can also be obtained through the diet. But it does not permeate easily through the blood-brain barrier (BBB), so the brain must supply their needs through the synthesis of creatine in the central nervous system (CNS) by itself. Creatine has a major role in maintaining stable levels of adenosine triphosphate (ATP) thus keeping the whole body in a proper condition. Neurodegenerative diseases leads to decreases in ATP levels, which compromises cellular metabolism, generating the increase of reactive species that could lead to neuronal cell death. Therefore, it becomes important to increase creatine levels in neurodegenerative diseases, so it could provide new alternative treatments for these diseases. This study aimed to develop and characterize liposomes with creatine, as well as investigate its protective effect in ischemia and reperfusion (I/R) brain model. Two methodologies were used for the preparation of liposomes, the lipid film hydration and ethanol injection. Due the best results were obtained by the ethanol injection method, this was chosen for the preparation of liposomes in in vivo tests. The rats were tested using I/R by clamping bilateral carotid arteries and different groups were treated with creatine (30 mg/kg) in free form (Liv+I/R) and liposomed (Lip+I/R) and compared with the control group and I/R. The animals motor activity, exploratory and memory abilities were evaluated through field tests and passive avoidance, 24 and 48 hours after I/R, respectively. After 72 hours, the animals were euthanized and the brains removed for biochemical determination of levels of reactive species and ascorbic acid (AA), and the biochemical breakdown activity of superoxide dismutase (SOD) and catalase (CAT). The suspensions of liposomes used for the in vivo treatment had homogenous average particle diameter (154 ± 6.9 nm), low polydispersity index (0.211 ± 0.019), pH near neutral (around 6.7), negative potential Zeta (-21 ± 1.8 mV) and association rate around 31%. The results of field tests have shown that I/R caused a change in exploratory activity of animals and increased oxidative stress in the brain of rats subjected to I/R. Liposomes creatine protected the change in exploratory activity and increased oxidative stress in rat cortex. Already in free form, creatine was not able to protect against these changes. With these results, we can conclude that the production of liposomes containing creatine technological feasibility presented, demonstrating the potential to increase the bioavailability of creatine into the CNS via the BBB.A creatina é uma biomolécula sintetizada endogenamente a partir de aminoácidos, que também pode ser obtida através da dieta. Porém, ela não permeia facilmente através da barreira hematoencefálica (BHE), assim o cérebro deve suprir suas necessidades através da síntese de creatina no próprio sistema nervoso central (SNC). A grande importância da creatina para o funcionamento correto do organismo está em manter estáveis os níveis de adenosina trifosfato (ATP). Doenças neurodegenerativas levam a déficits de ATP, o que compromete o metabolismo celular, gerando espécies reativas (ERs) capazes de levar as células neuronais à morte. Assim, torna-se importante aumentar os níveis de creatina em doenças neurodegenerativas, podendo gerar novas alternativas de tratamento para estas doenças. Desta forma, o presente trabalho teve como objetivo desenvolver e caracterizar lipossomas de creatina, bem como, investigar o seu efeito protetor em um modelo de isquemia e reperfusão (I/R) cerebral. Foram utilizadas duas metodologias para o preparo dos lipossomas, a hidratação do filme lipídico e a injeção de etanol. Devido aos melhores resultados obtidos pelo método de injeção de etanol, este foi escolhido para o preparo dos lipossomas a serem aplicados nos testes in vivo. Os ratos foram submetidos ao processo de I/R pelo clampeamento bilateral das artérias carótidas, sendo os diferentes grupos tratados com a creatina (30 mg/kg) na forma livre (Liv+I/R) e lipossomada (Lip+I/R), sendo comparados com os grupos controle e I/R. A atividade locomotora, exploratória e a memória dos animais foram avaliadas através dos testes de campo aberto e da esquiva passiva, 24 e 48 h após a I/R, respectivamente. Após 72 h, os animais foram eutanasiados e os cérebros removidos para as determinações bioquímicas dos níveis de ERs e ácido ascórbico (AA), e a atividade das enzimas superóxido dismutase (SOD) e catalase (CAT). As suspensões de lipossomas utilizadas para o tratamento in vivo apresentaram diâmetro médio de partícula homogêneo (154 ± 6,9 nm), com baixo índice de polidispersão (0,211 ± 0,019), pH próximo a neutralidade (em torno de 6,7), potencial Zeta negativo (-21 ± 1,8 mV) e taxa de associação em torno de 31%. Os resultados do teste de campo aberto demonstraram que a I/R causou alteração na atividade exploratória dos animais. Além disso, o estudo demonstrou aumento no estresse oxidativo no cérebro de ratos submetidos a I/R. Os lipossomas de creatina protegeram a alteração na atividade exploratória e o aumento do estresse oxidativo em córtex de ratos. Já a creatina na forma livre não foi capaz de proteger contra estas alterações. Através destes resultados, pode-se concluir que a produção de lipossomas contendo creatina apresentou viabilidade tecnológica, demonstrando potencial para aumentar a biodisponibilidade de creatina para o SNC através da BHE.Made available in DSpace on 2018-06-27T18:56:03Z (GMT). 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dc.title.por.fl_str_mv |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
title |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
spellingShingle |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA Borin, Diego Becker lipossoma creatina barreira hematoencefálica (BHE) sistema nervoso central (SNC) liposome, creatine blood-brain barrier (BBB) central nervous system (CNS) CNPQ::ENGENHARIAS |
title_short |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
title_full |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
title_fullStr |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
title_full_unstemmed |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
title_sort |
EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA |
author |
Borin, Diego Becker |
author_facet |
Borin, Diego Becker |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Alves, Marta Palma |
dc.contributor.advisor1ID.fl_str_mv |
CPF:47427582004 |
dc.contributor.advisor-co1.fl_str_mv |
Luchese, Cristiane |
dc.contributor.advisor-co1ID.fl_str_mv |
CPF:00490362036 |
dc.contributor.authorID.fl_str_mv |
CPF:01459841093 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4217888H4 |
dc.contributor.author.fl_str_mv |
Borin, Diego Becker |
contributor_str_mv |
Alves, Marta Palma Luchese, Cristiane |
dc.subject.por.fl_str_mv |
lipossoma creatina barreira hematoencefálica (BHE) sistema nervoso central (SNC) |
topic |
lipossoma creatina barreira hematoencefálica (BHE) sistema nervoso central (SNC) liposome, creatine blood-brain barrier (BBB) central nervous system (CNS) CNPQ::ENGENHARIAS |
dc.subject.eng.fl_str_mv |
liposome, creatine blood-brain barrier (BBB) central nervous system (CNS) |
dc.subject.cnpq.fl_str_mv |
CNPQ::ENGENHARIAS |
description |
Creatine is a biomolecule endogenously synthesized from amino acids which can also be obtained through the diet. But it does not permeate easily through the blood-brain barrier (BBB), so the brain must supply their needs through the synthesis of creatine in the central nervous system (CNS) by itself. Creatine has a major role in maintaining stable levels of adenosine triphosphate (ATP) thus keeping the whole body in a proper condition. Neurodegenerative diseases leads to decreases in ATP levels, which compromises cellular metabolism, generating the increase of reactive species that could lead to neuronal cell death. Therefore, it becomes important to increase creatine levels in neurodegenerative diseases, so it could provide new alternative treatments for these diseases. This study aimed to develop and characterize liposomes with creatine, as well as investigate its protective effect in ischemia and reperfusion (I/R) brain model. Two methodologies were used for the preparation of liposomes, the lipid film hydration and ethanol injection. Due the best results were obtained by the ethanol injection method, this was chosen for the preparation of liposomes in in vivo tests. The rats were tested using I/R by clamping bilateral carotid arteries and different groups were treated with creatine (30 mg/kg) in free form (Liv+I/R) and liposomed (Lip+I/R) and compared with the control group and I/R. The animals motor activity, exploratory and memory abilities were evaluated through field tests and passive avoidance, 24 and 48 hours after I/R, respectively. After 72 hours, the animals were euthanized and the brains removed for biochemical determination of levels of reactive species and ascorbic acid (AA), and the biochemical breakdown activity of superoxide dismutase (SOD) and catalase (CAT). The suspensions of liposomes used for the in vivo treatment had homogenous average particle diameter (154 ± 6.9 nm), low polydispersity index (0.211 ± 0.019), pH near neutral (around 6.7), negative potential Zeta (-21 ± 1.8 mV) and association rate around 31%. The results of field tests have shown that I/R caused a change in exploratory activity of animals and increased oxidative stress in the brain of rats subjected to I/R. Liposomes creatine protected the change in exploratory activity and increased oxidative stress in rat cortex. Already in free form, creatine was not able to protect against these changes. With these results, we can conclude that the production of liposomes containing creatine technological feasibility presented, demonstrating the potential to increase the bioavailability of creatine into the CNS via the BBB. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-03-26 |
dc.date.accessioned.fl_str_mv |
2018-06-27T18:56:03Z |
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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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
BORIN, Diego Becker. EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA. 2013. 72 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2013. |
dc.identifier.uri.fl_str_mv |
http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/206 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/291 |
identifier_str_mv |
BORIN, Diego Becker. EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA. 2013. 72 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2013. |
url |
http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/206 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/291 |
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Universidade Franciscana |
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Mestrado Acadêmico em Nanociências |
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Biociências e Nanomateriais |
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Universidade Franciscana |
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