Iron Mobilisation and Cellular Protection by a New Synthetic Chelator O-Trensox
| Autor: | Nafissa Rakba, Fouad Aouad, Paul Baret, Roberta J. Ward, Isabelle Morel, Catherine Caris, Gérard Lescoat, Pierre Brissot, Christophe Henry, Jean-Louis Pierre, Robert R. Crichton |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Iron Aspartate transaminase Hemosiderin Deferoxamine In Vitro Techniques Iron Chelating Agents Ferric Compounds Biochemistry chemistry.chemical_compound In vivo Lactate dehydrogenase Ethylamines medicine Animals Chelation Rats Wistar Cells Cultured Pharmacology biology Chemistry Molecular biology Rats Ferritin medicine.anatomical_structure Liver Alanine transaminase Hepatocyte Ferritins Hydroxyquinolines biology.protein Iron-Dextran Complex medicine.drug |
| Zdroj: | Biochemical Pharmacology. 55:1797-1806 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/s0006-2952(98)00009-4 |
| Popis: | We tested a new synthetic, 8-hydroxyquinoline-based, hexadentate iron chelator, O-Trensox and compared it with desferrioxamine B (DFO). Iron mobilisation was evaluated: (i) in vitro by using ferritin and haemosiderin; DFO mobilised iron much more rapidly from ferritin at pH 7.4 than did O-Trensox, whereas at pH 4, ferritin and haemosiderin iron mobilisation was very similar with both chelators; (ii) in vitro by using cultured rat hepatocytes which had been loaded with Fe-55-ferritin; here DFO was slightly more effective after 100 hr than O-Trensox; (iii) in vivo administration i.p. to rats which had been iron-loaded with iron dextran; O-Trensox mobilised 51.5% of hepatic iron over two weeks compared to 48.8% for DFO. We also demonstrated the effect of O-Trensox in decreasing the entry of Fe-55 citrate into hepatocyte cultures. The protective effect of O-Trensox against iron toxicity induced in hepatocyte cultures by ferric citrate was shown by decreased release of the enzymes lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotranferase (ALT) from the cultures and, using electron paramegnetic resonance (EPR) measurements, decreased production of lipid radicals. O-Trensox was more effective than DFO in quenching hydroxyl radicals in an acellular system. (C) 1998 Elsevier Science Inc. |
| Databáze: | OpenAIRE |
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