AVALIAÇÃO DO EFEITO PROTETOR DE SINVASTATINA NA FORMA LIVRE E NANOENCAPSULADA EM CONVULSÕES INDUZIDAS POR ÁCIDO QUINOLÍNICO EM RATOS

• Ano de defesa: 2015
• Autor(a) principal: Alves, Catiane Bisognin
• Orientador(a): Boeck, Carina Rodrigues
• Banca de defesa: Schmidt, André Prato, Fernandes, Liana da Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Centro Universitário Franciscano
• Programa de Pós-Graduação: Programa de Pós-Graduação em Nanociências
• Departamento: Biociências e Nanomateriais
• País: Brasil
• Palavras-chave em Português: nanotecnologia; neuroproteção; sinvastatina; convulsões; ácido quinolínico.
• Palavras-chave em Inglês: nanotechnology; neuroprotection; simvastatin; seizures; acid quinolinic
• Área do conhecimento CNPq: Biociências e Nanomateriais
• Link de acesso: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/534

Statins are cholesterol-lowering agents due to the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Recent studies have shown pleiotropic effects for statins, such as anti-epileptic effect in rodents. Quinolinic acid (QA) is an endogenous glutamate analog that may be involved in the etiology of epilepsy and is related to disturbances on glutamate release and uptake. The nanoparticles have become an important focus of therapeutic research on brain because they are an especially effective form of drug delivery. Therefore, considering the therapeutic potentials of nanocapsules, in the present study the protective effect of simvastatin in nanoencapsulated (SN) or free form (SF) is evaluated in QA-induced seizures in rats. Male adult Wistar rats (250-300 g) were pretreated orally during 21 days with control formulation (drug-unloaded NCs, CF), SN or SF at 1 mg/kg/day. After pretreatment, rats were infused with 4 μL of 239.2 nmol QA at right lateral brain ventricle and observed for behavioral changes during 10 min. Twenty four hours after seizures, rats were evaluated for locomotion, balance, gait and memory. CF had pH 6.75 ± 0.19, particle diameter of 213.91 ± 19.96 nm, polydispersity index of 0.167 ± 0.05 and zeta-potential values were -16,28 ± 7,90. SN had pH 6.68 ± 0.25, particle diameter of 215.25 ± 30.58 nm, polydispersity index of 0.151 ± 0.07 and zeta potential values were -16.13 ± 8.19 mV. The body weight of rats did not change during the treatment period. The pretreatment com SN or SF did not change the seizures or number of death following QA infusion. In the group CF + QA the number of rats with fall in the Beam Balance task was higher than Naive group, effect prevented by SN and SF. The groups CF + Sal and SF + QA showed a reduced number of rearings in the Open Field test, besides the increased stride length in the Footprint test. Rats infused with SF + QA had impairment of memory in the Avoidance Inhibitory Memory task and SN or SF did not change this damage effect. Altogether, the present results exhibit that simvastatin in nanoencapsulated or free form at the dose 1 mg/kg/day administered for 21 days was not able to protect rats against the behavioral damages induced by QA in rats (with exception on balance parameter). Another strategies need to investigate to better evaluate the effect of nanocapsules against cerebral damage induced by QA.