Srichairatanakool S, Thephinlap C, Phisalaphong C, Porter J B, Fucharoen S
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Med Chem. 2007 Sep;3(5):469-74. doi: 10.2174/157340607781745447.
Non-transferrin-bound iron (NTBI) is detectable in plasma of beta-thalassemia patients with transfusional iron overload. This form of iron may cause oxidative tissue damage and increased iron uptake, into several vital organs. Removal of NTBI species is incomplete and transient using standard intermittent desferrioxamine (DFO) or deferiprone (DFP) monotherapy. Combinations of these or other chelators may improve the protection time from NTBI and increase removal of harmful NTBI species. Curcuminoids from Curcuma longa L. is a naturally occurring phytochemical which shows a wide range of pharmacological properties including anti-oxidative, anti-inflammatory, anti-cancer and iron-chelating activities. In this study, the curcuminoids was investigated for NTBI chelation in thalassemic plasma in vitro and for the potential to improve NTBI removal when used with other chelators. Curcumin bound Fe(3+) to form a Fe(3+)-curcumin complex with a predominant absorption at 500 nm. The chemical binding of curcumin was dose- and time-dependent and more specific for Fe(3+) than Fe(2+). Using a HPLC-based NTBI assay without an aluminium blocking step, curcumin shuttled the iron from Fe(3+)-NTA complex, giving underestimated NTBI values. At equivalent concentrations DFO, DFP and curcumin decreased plasma NTBI with the order of DFP>DFO>curcumin. None of these chelators removed NTBI completely, but curcumin appeared to increase the rate of NTBI removal when added to DFP. It is proposed that the beta-diketo moiety of curcumin participates in the NTBI chelation.
在因输血导致铁过载的β地中海贫血患者的血浆中可检测到非转铁蛋白结合铁（NTBI）。这种形式的铁可能会导致氧化组织损伤，并增加铁向多个重要器官的摄取。使用标准的间歇性去铁胺（DFO）或去铁酮（DFP）单一疗法去除NTBI并不完全且是短暂的。这些螯合剂或其他螯合剂的组合可能会延长对NTBI的保护时间，并增加对有害NTBI种类的清除。姜黄中的姜黄素是一种天然存在的植物化学物质，具有广泛的药理特性，包括抗氧化、抗炎、抗癌和铁螯合活性。在本研究中，研究了姜黄素在体外对地中海贫血患者血浆中NTBI的螯合作用，以及与其他螯合剂联合使用时改善NTBI清除的潜力。姜黄素与Fe(3+)结合形成Fe(3+)-姜黄素复合物，并在500 nm处有主要吸收峰。姜黄素的化学结合具有剂量和时间依赖性，对Fe(3+)的特异性高于Fe(2+)。使用基于高效液相色谱的NTBI测定法且无铝阻断步骤时，姜黄素将铁从Fe(3+)-NTA复合物中转运出来，导致NTBI值被低估。在等效浓度下，DFO、DFP和姜黄素降低血浆NTBI的顺序为DFP>DFO>姜黄素。这些螯合剂均不能完全去除NTBI，但姜黄素添加到DFP中时似乎能提高NTBI的清除率。有人提出姜黄素的β-二酮部分参与了NTBI的螯合作用。
