|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Caratterizzazione di nuovi complessi di Zinco ed aminoacidi per la distribuzione di Zinco in cellule Caco-2|
|Titolo in inglese||Characterization of novel Zinc amino acid complexes for Zinc delivery using Caco-2 cells|
|Struttura||Dipartimento di Scienze della Vita|
|Corso di studi||CHIMICA E TECNOLOGIA FARMACEUTICHE (D.M. 270/04)|
|Data inizio appello||2016-11-03|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
I disturbi dello spettro autistico (ASD) sono un gruppo di disturbi dello sviluppo neurologico caratterizzato da menomazioni nella comunicazione e nel comportamento sociale.
Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders characterized by impairments in communication and social behavior. It is generally accepted that a variety of environmental risk factors and genetic factors in combination or alone are associated with the etiology of autism spectrum disorders. As Zinc deficiency has been linked to ASD, it is necessary to keep adequate Zinc levels, exspecially during pregnancy. However, the bioavailability of Zinc in the diet is low and might be overcome by novel supplements. In this study, the influence of Zinc supplementation with amino acid-Zinc compound in Caco-2 cells was investigated. To maintain Zinc steady status different mechanism or factors to regulate Zinc absorption and efflux are necessary. In this project we focused on how to medicate Zn deficiency associated with diseases like autism and acrodermatitis enteropathica. The purpose was to design novel Zn compounds, able to bypass inhibitory factors and to evade routes potentially saturated by Zn, such as classic Zn transporters. In particular, we explored Zip4, since it is also highly associated with Acrodermatitis enteropathica, a genetic disorder of Zinc delivery. Accordingly, as Zinc compounds and ZnCl2 could use different way of absorption, we investigate which is better absorbed. We prepared Zn linked to AAs, subsequently we studied the efficiency and characterization in Caco-2 cells of Zn uptake. We treated colon epithelial cells with different Zinc compounds and a Zinc solution to compare compounds or ZnCl2. The bioavailability of Zn in supplements is influenced by multiple factors that can decrease Zinc absorption (Cousins, 2010). We investigated the influence of inhibitors as Cu, Ca, phytic acids and folic acids. Inhibitors were utilized in simultaneity with Zn compounds. After proving that Zinc is taken up, we examined the absorption and transport of Zinc compounds in Caco-2 cells using transwell plates, but we determined that the used transwell are not optimal for our studies. The idea is to develop Zinc delivery compounds able to bypass normal Zinc transporters using AAs transporters without involving their down regulation. Moreover, we studied if there are changes in gene expression of Zinc and AA transporters as compensatory mechanism specific to various substances. In this project ZIP4, ZIP2 and ZnT1 were used to examine possible alterations in gene expression and protein translation, after treatment of Caco-2 cell with different Zinc compounds. We concluded that one of the benefits of novel Zinc delivery compounds complexed with amino acids, are that they can be used as Zinc supplement during chronic therapy without modifying normal physiological reactions. Taken together these experiments illustrate characteristics and mechanisms of Zinc supplementation with amino Zinc-acids compounds. The determination of the importance to medicate Zinc deficiency can be useful suggesting therapeutics strategies for prevention of ASD.