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Statements

Subject Item
n2:RIV%2F61389013%3A_____%2F14%3A00431233%21RIV15-GA0-61389013
rdf:type
n14:Vysledek skos:Concept
dcterms:description
Wilson’s disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson’s disease. Wilson’s disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson’s disease.
dcterms:title
Chelating polymeric beads as potential therapeutics for Wilson’s disease Chelating polymeric beads as potential therapeutics for Wilson’s disease
skos:prefLabel
Chelating polymeric beads as potential therapeutics for Wilson’s disease Chelating polymeric beads as potential therapeutics for Wilson’s disease
skos:notation
RIV/61389013:_____/14:00431233!RIV15-GA0-61389013
n3:aktivita
n17:P n17:I
n3:aktivity
I, P(ED0030/01/01), P(FR-TI4/625), P(GA13-08336S), P(GAP304/12/0950)
n3:cisloPeriodika
1 October
n3:dodaniDat
n11:2015
n3:domaciTvurceVysledku
n4:6593534 n4:1474545 n4:2540568 n4:2095653 Vetrík, Miroslav
n3:druhVysledku
n16:J
n3:duvernostUdaju
n9:S
n3:entitaPredkladatele
n18:predkladatel
n3:idSjednocenehoVysledku
7063
n3:idVysledku
RIV/61389013:_____/14:00431233
n3:jazykVysledku
n15:eng
n3:klicovaSlova
Wilson’s disease; polymer beads; chelators
n3:klicoveSlovo
n5:Wilson%E2%80%99s%20disease n5:polymer%20beads n5:chelators
n3:kodStatuVydavatele
NL - Nizozemsko
n3:kontrolniKodProRIV
[D1DA3626D38D]
n3:nazevZdroje
European Journal of Pharmaceutical Sciences
n3:obor
n12:CA
n3:pocetDomacichTvurcuVysledku
5
n3:pocetTvurcuVysledku
10
n3:projekt
n13:GAP304%2F12%2F0950 n13:FR-TI4%2F625 n13:GA13-08336S n13:ED0030%2F01%2F01
n3:rokUplatneniVysledku
n11:2014
n3:svazekPeriodika
62
n3:tvurceVysledku
Nový, Z. Mattová, J. Škodová, Michaela Hrubý, Martin Štěpánek, Petr Kučka, Jan Vetrík, Miroslav Urbánek, P. Petřík, M. Poučková, P.
n3:wos
000340301500001
s:issn
0928-0987
s:numberOfPages
7
n7:doi
10.1016/j.ejps.2014.05.002