caa a22 4500 445377593 CHVBK 20180317143007.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00702-010-0531-3 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0531-3 Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson's disease after peripheral administration [Elektronische Daten] [David Dexter, Sarah Statton, Charlotte Whitmore, Wolfhardt Freinbichler, Peter Weinberger, Keith Tipton, Laura Della Corte, Roberta Ward, Robert Crichton] The iron content of the substantia nigra pars compacta increases in the brains of Parkinson's disease patients. Hence, its removal by iron chelators may retard the progression of the disease. However, information on the ability of clinically available iron chelators to cross the blood brain barrier and be neuroprotective is limited. In this present study three iron chelators, which are currently approved for clinical use, namely the hexadendate, deferrioxamine, the bidentate deferiprone and the tridendate chelator deferasirox have been investigated for their efficacy to induce neuroprotection. Previous studies have shown that both deferiprone and deferrioxamine exert neuroprotection in the 6-hydroxy dopamine (6-OHDA) model but no such studies have investigated deferasirox. Focal administration of deferasirox (0.5, 2 and 10μg) into the substantia nigra pars compacta of rats significantly attenuated the loss of dopaminergic neurons and striatal dopamine content resulting from 6-OHDA toxicity. Systemic administration of deferasirox (20mg/kg), deferiprone (10mg/kg) or deferrioxamine (30mg/kg), to the 6-OHDA rat model of Parkinson's disease, significantly attenuated the loss of dopaminergic neurons and striatal dopamine content. Further studies to comprehend the action of these chelators showed that local application of either 0.4mM deferrioxamine, or 1mM deferasirox, via a microdialysis probe into the striatum, prior to that of 200μM 6-OHDA, prevented the generation of hydroxyl radicals. Our results confirm that the administration of these chelators show therapeutic efficacy and should be considered as therapeutic agents for the treatment of Parkinson's disease. Springer-Verlag, 2010 Iron chelators nationallicence Desferrioxamine nationallicence Deferasirox nationallicence Deferiprone nationallicence Brain iron nationallicence Parkinson's disease nationallicence Dexter David Centre for Neuroscience, Imperial College London, London, UK aut Statton Sarah Centre for Neuroscience, Imperial College London, London, UK aut Whitmore Charlotte Centre for Neuroscience, Imperial College London, London, UK aut Freinbichler Wolfhardt Institute for Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria aut Weinberger Peter Institute for Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria aut Tipton Keith Biochemical Department, Trinity College, Dublin, Ireland aut Della Corte Laura Dipartimento di Farmacologia Preclinica e Clinica M. Aiazzi Mancini, Universita degli Studi di Firenze, Florence, Italy aut Ward Roberta Centre for Neuroscience, Imperial College London, London, UK aut Crichton Robert University Catholique de Louvain, 1 Croix de Sud, 1348, Louvain-la-Neuve, Belgium aut Journal of Neural Transmission Springer Vienna 118/2(2011-02-01), 223-231 0300-9564 118:2<223 2011 118 702 https://doi.org/10.1007/s00702-010-0531-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0531-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dexter David Centre for Neuroscience, Imperial College London, London, UK aut NATIONALLICENCE 700 1- Statton Sarah Centre for Neuroscience, Imperial College London, London, UK aut NATIONALLICENCE 700 1- Whitmore Charlotte Centre for Neuroscience, Imperial College London, London, UK aut NATIONALLICENCE 700 1- Freinbichler Wolfhardt Institute for Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria aut NATIONALLICENCE 700 1- Weinberger Peter Institute for Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria aut NATIONALLICENCE 700 1- Tipton Keith Biochemical Department, Trinity College, Dublin, Ireland aut NATIONALLICENCE 700 1- Della Corte Laura Dipartimento di Farmacologia Preclinica e Clinica M. Aiazzi Mancini, Universita degli Studi di Firenze, Florence, Italy aut NATIONALLICENCE 700 1- Ward Roberta Centre for Neuroscience, Imperial College London, London, UK aut NATIONALLICENCE 700 1- Crichton Robert University Catholique de Louvain, 1 Croix de Sud, 1348, Louvain-la-Neuve, Belgium aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/2(2011-02-01), 223-231 0300-9564 118:2<223 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer