An animal model of iron overload and its application to study hepatic ferritin iron mobilization by chelators |
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| Authors: | A Longueville R R Crichton |
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| Affiliation: | 1. Department of Imaging, Rennes University Hospital, Rennes, France;2. INSERM, UMR 1099, Rennes F-35000, France;3. Université de Rennes 1, LTSI, Rennes F-35000, France;4. CRLCC, Centre Eugène Marquis, Rennes F-35000, France;1. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu, China;2. Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China;1. Institute of Experimental and Translational Cardiac Imaging, DZHK Centre for Cardiovascular Imaging, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany;2. Department of Haematology and Oncology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany;3. Department of Cardiology, University Hospital La Paz, Madrid, Spain;4. Department of Cardiology, Universiti Teknologi MARA (UiTM), Sg. Buloh, Malaysia;5. Department of Radiology, XiangYa Hospital, Central South University, Changsha, Hunan, China;6. Department of Biomedical Sciences and Morphological and Functional Imaging, G. Martino University Hospital Messina, Italy;7. Department of Cardiology, Menzies Institute for Medical Research, University of Tasmania, Australia;8. Department of Radiology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany;9. Department of Cardiology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany;10. Department of Cardiology, Guys and St Thomas'' NHS Trust, London, United Kingdom |
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| Abstract: | Administration of 3,5,5-trimethylhexanoyl ferrocene in the diet of male Wistar rats results in a substantial increase in hepatic ferritin protein (greater than 2-fold) and of ferritin iron (4-8-fold). The iron-loading in liver, under the conditions used, appears to be essentially in parenchymal cells rather than in reticulo-endothelial cells. It is suggested that the model represents a useful system for the study of the potential efficacy of new iron chelators for the mobilization of hepatic storage iron. The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload. Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally. Our studies lead to the conclusion that DFT merits further examinations, for its activity as an orally active iron chelator. |
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