RESUMO
Quercetin has been identified as a promising compound with a neuroprotective potential against age-related neurodegenerative diseases such as Alzheimer's disease (AD). Nevertheless, the clinical application of quercetin is hampered by its low oral bioavailability. The aim of this work was to evaluate the capability of nanoencapsulated quercetin in zein nanoparticles (NPQ), that significantly improves the oral absorption and bioavailability of the flavonoid, as potential oral treatment for AD. For this purpose, SAMP8 mice were orally treated for two months with either NPQ (25mg/kg every 48h) or a solution of quercetin (Q; 25mg/kg daily). NPQ displayed a size of 260nm and a payload of about 70µg/mg. For Q, no significant effects were observed in animals. On the contrary, the oral administration of NPQ improved the cognition and memory impairments characteristics of SAMP8 mice. These observations appeared to be related with a decreased expression of the hippocampal astrocyte marker GFAP. Furthermore, significant levels of quercetin were quantified in the brain of mice treated with nanoparticles. These findings highlight the potential of zein nanoparticles to promote the oral absorption of quercetin as well as the therapeutic potential of this flavonoid in AD pathogenesis.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Portadores de Fármacos/química , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Quercetina/uso terapêutico , 2-Hidroxipropil-beta-Ciclodextrina , Administração Oral , Doença de Alzheimer/psicologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacocinética , Tamanho da Partícula , Quercetina/administração & dosagem , Quercetina/farmacocinética , Teste de Desempenho do Rota-Rod , Zeína/química , beta-Ciclodextrinas/químicaRESUMO
Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, but deterioration of renal function also correlates with tubular alterations. Human DN is characterized by glycogen accumulation in tubules. Although this pathological feature has long been recognized, little information exists about the triggering mechanism. In this study, we detected over-expression of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced expression suggests the participation of MGS in renal metabolic changes associated with diabetes. HK2 human renal cell line exhibited an intrinsic ability to synthesize glycogen, which was enhanced after over-expression of protein targeting to glycogen. A correlation between increased glycogen amount and cell death was observed. Based on a previous transcriptome study on human diabetic kidney disease, significant differences in the expression of genes involved in glycogen metabolism were analyzed. We propose that glucose, but not insulin, is the main modulator of MGS activity in HK2 cells, suggesting that blood glucose control is the best approach to modulate renal glycogen-induced damage during long-term diabetes.