AVALIAÇÃO DE LIPOSSOMAS COM CREATINA SOBRE O METABOLISMO CEREBRAL DE RATOS WISTAR COM HIPERFENILALANINEMIA

• Autor(a) principal: Mezzomo, Nathana Jamille
• Data de Publicação: 2015
• 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/535
• topic: Nanotecnologia. Erros inatos do metabolismo. Comportamento. Estresse oxidativo.; Nanotechnology. Inborn errors of metabolism. Behavior. Oxidative stress; Biociências e Nanomateriais

Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by a deficiency of hepatic phenylalanine hydroxylase enzyme (EC 1.14.16.1 - PAH), which converts Phe tyrosine (Tyr), resulting in hyperphenylalaninemia. Excess Phe compromises the developing brain of affected individuals. Considering the creatine energy and neuroprotective substance, the aim of use it in liposomal form was to increase its concentration in the brain and evaluate parameters of energy metabolism, oxidative stress and behavioral usually changed by excess Phe in PKU patients or hyperphenylalaninemia (HPA) animals. Also, check whether the administrations of nanoparticles could affect non-PAH rats parameters, thus evaluating a neurotoxic action. The ethanol injection method for production of liposomes containing creatine allowed the formation of nanoscale particles with pH around the saline, with an average size of 236.44 nm, a polydispersity index below 0.3, mean zeta potential of -23.9 mV, encapsulation efficiency of 33.65% and creatine content of 93%. The HPA alter the activity of cytosolic and mitochondrial fractions of creatine kinase (CK) in the cerebral cortex and the hippocampus in the mitochondrial fraction, however, did not affect the activity of pyruvate kinase (PK) and adenilato kinase (AK) the analyzed brain structures. The administration of liposomes containing creatine (LCr) possibly prevented the alterations of cytosolic and mitochondrial CK activity in the cerebral cortex of the HPA group. Induction HPA did not change the oxidative stress parameters evaluated in the brain cortex and hippocampus. However, administration of LCr in animals non-HPA, increased levels of GSH antioxidant and superoxide dismutase activity (SOD) and in contrast, stimulated an increased of dihydrodichlorofluorescein oxidation (DCFH) in cerebral cortex. The blank liposomes (LBr) also increased the reduced glutathione (GSH) content in the cerebral cortex. Associated with these results, one can also check the cerebral impairment of the HPA animals through the reduced brain mass, open field test, tail suspension and elevated zero maze. The administration of LCr the HPA animals can partially prevent changes in enzyme activity, as well as the number of rearings improved open field test and the number of head-dipping of the elevated zero maze test. In short, we believe that the LCr may have crossed the blood-brain barrier, since its effects were differentiated administration of free creatine (Cr), thus preventing changes caused by Phe administration on behavioral tests and enzyme activity energy metabolism in the cortex and hippocampus.