Labile plasma iron in iron overload: redox activity and susceptibility to chelation
Labile plasma iron in iron overload: redox activity and susceptibility to chelation
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DOI：
10.1182/blood-2003-03-0807
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发表时间：
2003-10-01
期刊：
影响因子：
20.3
通讯作者：
Cabantchik, ZI
中科院分区：
文献类型：
--
作者：
Esposito, BP;Breuer, W;Cabantchik, ZI
血浆非转铁蛋白结合铁（NTBI）被认为是负责催化铁超载受试者循环中活性自由基的形成，导致氧化产物的积累。我们评估了健康和地中海贫血患者血浆中NTBI的氧化还原活性成分。通过监测由抗坏血酸引起但被铁螯合剂阻断的活性自由基的产生，用荧光二氢膦胺123测定血浆不稳定铁（LPI）。该试验是LPI特异性的，因为它是由抗坏血酸的生理浓度产生的，不涉及样品操作，并且被选择性结合铁的铁螯合剂阻断。健康人血清中基本不存在LPI，但β -地中海贫血患者血清中的LPI水平（1-16 muM）与NTBI中以动员剂依赖性螯合铁或去铁胺螯合铁测量的水平显著相关。口服去铁素（L1）患者由于铁动员而升高血浆NTBI，但未导致LPI出现，表明血浆中L1螯合铁不具有氧化还原活性。此外，口服L1治疗消除了患者的LPI。该方法可以评估LPI对体内或体外螯合的敏感性，以及在铁过载条件下LPI引起组织损伤的可能性。(C) 2003年由美国血液病学会出版。
Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for catalyzing the formation of reactive radicals in the circulation of iron overloaded subjects, resulting in accumulation of oxidation products. We assessed the redox active component of NTBI in the plasma of healthy and beta-thalassemic patients. The labile plasma iron (LPI) was determined with the fluorogenic dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted by ascorbate but blocked by iron chelators. The assay was LPI specific since it was generated by physiologic concentrations of ascorbate, involved no sample manipulation, and was blocked by iron chelators that bind iron selectively. LPI, essentially absent from sera of healthy individuals, was present in those of beta-thalassemla patients at levels (1-16 muM) that correlated significantly with those of NTBI measured as mobilizer-dependent chelatable iron or desferrioxamine chelatable iron. Oral treatment of patients with deferiprone (L1) raised plasma NTBI due to iron mobilization but did not lead to LPI appearance, indicating that L1-chelated iron in plasma was not redox active. Moreover, oral L1 treatment eliminated LPI in patients. The approach enabled the assessment of LPI susceptibility to in vivo or in vitro chelation and the potential of LPI to cause tissue damage, as found in iron overload conditions. (C) 2003 by The American Society of Hematology.