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• W1965822298 abstract "Bidentate hydroxypyridinone chelators effectively complex and facilitate excretion of trivalent iron. To test the hypothesis that hexadentate chelators are more effective than bidentate chelators at low concentrations, urinary and biliary Fe excretions were determined in Fe-loaded rats before and after administration of a bidentate chelator, Pr-(Me-3,2-HOPO), or its hexadentate analogue, TREN-(Me-3,2-HOPO). The bidentate chelator slightly increased biliary Fe excretion in Fe-loaded rats after IV (90 micromol/kg) and PO (90 or 270 micromol/kg) administration, but chelation efficiency did not exceed 1%. The hexadentate chelator markedly increased biliary Fe excretion, achieving overall chelation efficiencies of 14% after IV administration of 30 micromol/kg and 8 or 3% after PO (30 or 90 micromol/kg) administration. The hexadentate chelator was significantly more effective than the bidentate chelator after IV injection and oral dosing. In chelator-treated Fe-loaded or saline-injected rats, >90% of the excreted Fe was in the bile. Oral TREN-(Me-3,2-HOPO), given to non-Fe-loaded rats, did not appreciably change Fe output, indicating that there was little Fe depletion in the absence of Fe overload. These results support the hypothesis that greater Fe chelation efficiency can be achieved with hexadentate than with bidentate chelators at lower, and presumably safer, concentrations. The results also demonstrate that TREN-(Me-3, 2-HOPO) is a promising, orally effective, Fe chelator." @default.
• W1965822298 created "2016-06-24" @default.
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• W1965822298 date "2000-04-01" @default.
• W1965822298 modified "2023-10-17" @default.
• W1965822298 title "The Hexadentate Hydroxypyridinonate TREN‐(Me‐3,2‐HOPO) is a More Orally Active Iron Chelator Than Its Bidentate Analogue" @default.
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• W1965822298 doi "https://doi.org/10.1002/(sici)1520-6017(200004)89:4<545::aid-jps12>3.0.co;2-j" @default.
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