EFEITO ANTIOXIDANTE DE LIPOSSOMAS CONTENDO CREATINA NO PROCESSO DE ISQUEMIA/REPERFUSÃO CEREBRAL EM RATOS: DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO FARMACOLÓGICA

• Ano de defesa: 2013
• Autor(a) principal: Borin, Diego Becker
• Orientador(a): Alves, Marta Palma
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Franciscana
• Programa de Pós-Graduação: Mestrado Acadêmico em Nanociências
• Departamento: Biociências e Nanomateriais
• País: BR
• Palavras-chave em Português: lipossoma; creatina; barreira hematoencefálica (BHE); sistema nervoso central (SNC)
• Palavras-chave em Inglês: liposome, creatine; blood-brain barrier (BBB); central nervous system (CNS)
• Área do conhecimento CNPq: CNPQ::ENGENHARIAS
• Link de acesso: http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/206; http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/291

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.