Quintosana e seus derivados conjugados com ?cido g?lico: avalia??o de seu potencial antioxidante e de interfer?ncia na forma??o de cristais de oxalato de c?lcio

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Bibliographic Details
Main Author: Queiroz Neto, Moacir Fernandes de
Other Authors: 76111830449
Language:Portuguese
Published: Universidade Federal do Rio Grande do Norte 2016
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Online Access:http://repositorio.ufrn.br/handle/123456789/19620
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No. of bitstreams: 1 MoacirFernandesDeQueirozNeto_DISSERT.pdf: 2451986 bytes, checksum: 86a4ed116bac73f635a0765a8cdd98c9 (MD5) Previous issue date: 2014-12-11 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq === Quitina ? segundo polissacar?deo mais abundante na natureza e seu derivado quitosana tem sido amplamento estudado, devido a suas propriedades qu?micas e farmacol?gicas singulares. Contudo, estudos mostram que essa mol?cula quando no organismo, tende a se acumular no tecido renal e tamb?m promove um aumento na excre??o de c?lcio. Apesar disso, o efeito da quitosana sobre a forma??o de cristais de oxalato de c?lcio (OxCa) nunca foi avaliado. A forma??o de c?lculos renais (urolit?ase) ? a enfermidade que mais comumente afeta os rins e o sistema urin?rio, al?m de ser uma doen?a que possui altas preval?ncia e recorr?ncia. Muitas mol?culas com capacidade antioxidante tem demonstrado potencial para diminuir a forma??o de cristais de OxCa in vitro. Diante do exposto o objetivo desse trabalho foi avaliar o potencial antioxidante e de interfer?ncia na forma??o de cristais de uma quitosana de baixo peso molecular e seus derivados conjugados com ?cido g?lico (AG). As analises f?sico-qu?micas confirmaram a identidade da quitosana. Esta foi submetida a 5 testes antioxidantes e apresentou uma excelente atividade quelante de cobre, por?m nenhuma outra atividade antioxidante expressiva foi detectada. J? quando submetida aos testes de forma??o de cristais in vitro, a quitosana aumentou o n?mero de cristais de OxCa monohidratados formados, modificou a morfologia desses cristais, modificou as propor??es entre popula??es de cristais em solu??o e aumentou o potencial zeta desses cristais formados. Foram obtidas quatro mol?culas de quitosana conjugadas com AG. As an?lises f?sico-qu?micas confirmaram que houve liga??o covalente entre quitosana e AG, por?m, n?o se observou uma conjuga??o de AG de forma dose-dependente. Quando estes derivados foram submetidas a testes antioxidantes, todas as quitosanas conjugadas apresentaram potencial antioxidante maior que seus percussores. Contudo, houve diferen?a de atividade entre as diferentes quitosanas conjugadas, indicando que a posi??o onde o AG est? conjugado ? um fator importante para determina??o da atividade. Quando as quitosanas conjugadas foram submetidas aos testes de forma??o de cristais in vitro, houve uma redu??o na quantidade de cristais observados quando comparados com aqueles formados na presen?a da quitosana n?o-conjugada. A quitosana possui uma forte capacidade indutora de forma??o de cristais de OxCa monohidratados, bem como modifica sua morfologia e potencial zeta. O processo de conjuga??o de AG ? quitosana levou a um aumento no potencial antioxidante dessa mol?cula e tamb?m foi capaz de diminuir sua capacidade de induzir ? forma??o de cristais in vitro === Chitin is the second most abundant polysaccharide in nature and its derivative chitosan has been widely studied due to its unique chemical and pharmacological properties. However, studies show that when this molecule is used as food, drug, etc. it tends to accumulate in renal tissue and promotes an increase in calcium excretion. Nevertheless, the effect of chitosan on the formation of calcium oxalate (OxCa) crystals has never been evaluated. The formation of kidney stones (urolithiasis) is the disease that most often affects the kidneys and the urinary system. In addition, this is a disease with high prevalence and recurrence. Many molecules with antioxidant activity have been shown to decrease the potential for in vitro OxCa crystals formation. Thus, the aim of this study was to evaluate the effect of low molecular weight chitosan and its derivatives conjugated to gallic acid (AG) as antioxidant and inhibitor of OxCa crystals formation. The physico-chemical analysis confirmed the identity of chitosan. This molecule was subjected to five antioxidant tests and showed an excellent copper chelating activity. However, chitosan did not show other significant antioxidant activity. When chitosan was subjected to in vitro crystal formation tests, it increased the number of OxCa monohydrate crystals, modified the morphology of the crystals, modified the proportions between populations of crystals in solution and increased the zeta potential of these crystals formed. Four molecules of chitosan conjugated with GA were obtained. The physico-chemical analysis confirmed that chitosan and AG were covalently bonded. However, the amount of GA liked to chitosan did not increase even when 10 times more GA was used in experiment. When these derivatives were subjected to antioxidant tests, all chitosan conjugates showed higher antioxidant potential than their precursors. However, they showed different activity between them, which indicating that the position where AG is conjugated is an important factor for chitosan-GA activity. When conjugated chitosans were submitted to in vitro crystal formation tests, a reduction in the crystals number was observed when compared with those formed in the presence of unconjugated chitosan. Chitosan has a strong capacity for inducing OxCa monohydrate crystal formation, as well as modify their morphology and zeta potential. Over all, the process of conjugating AG to chitosan led to an increase in antioxidant potential of this molecule and was also able to decrease its capacity of inducing in vitro crystal formation