INTERACTIONS OF HYDROXYCARBAMIDE (HYDROXYUREA) WITH IRON AND COPPER: IMPLICATIONS ON TOXICITY AND THERAPEUTIC STRATEGIES
INTERACTIONS OF HYDROXYCARBAMIDE (HYDROXYUREA) WITH IRON AND COPPER: IMPLICATIONS ON TOXICITY AND THERAPEUTIC STRATEGIES
复制标题
DOI：
10.3109/03630269.2011.578950
复制
发表时间：
2011-01-01
期刊：
影响因子：
1
通讯作者：
Kontoghiorghes, George J.
中科院分区：
文献类型：
--
作者：
Konstantinou, Eleni;Pashalidis, Ioannis;Kontoghiorghes, George J.
初步的分光光度和电位研究表明，羟基尿素或羟基脲(HU)能与铜(II)、铁(II)、铁(II)和铁(III)离子形成络合物，例如在pH值为5时，HU与金属离子的比例为1HU：1。HU对铜(对数β1=3.1)和铁(对数β1=5)的亲和力远低于铁和铜络合药去铁酮(L1)，后者用于治疗铁负荷。预计在这些金属离子浓度较高的特定条件下，例如在输血铁超载的情况下，HU的治疗、药理和毒理特性可能会受到影响。也有人认为，过量的可螯合和不稳定形式的铁或铜离子，如非转铁蛋白结合铁(NTBI)或细胞内低分子活化铁，可能是导致癌症、镰状细胞性贫血、中间地中海贫血和其他组患者对HU疗效不同的主要因素。在体外、体内和临床条件下，HU与金属离子的相互作用机制还需要进一步的研究。
Preliminary spectrophotometric and potentiometric studies have shown that hydroxycarbamide or hydroxyurea (HU) can interact with copper(II) [Cu(II)], iron(II) [ Fe(II)] and Fe(III) ions and form complexes, for example, a ratio of 1 HU: 1 metal at pH 5. The affinity for Cu (log beta 1 = 3.1) and Fe (log beta 1 = 5) by HU is much lower than that of the Fe and Cu chelating drug deferiprone (L1), which is used for the treatment of iron overload. It is anticipated that under certain conditions of high concentrations of these metal ions such as in transfusional iron overload, the therapeutic, pharmacological and toxicological properties of HU could be affected. It is also suggested that excess chelatable and labile forms of Fe or Cu ions, such as non transferrin-bound iron (NTBI) or intracellular low molecular weight labile iron, are among the main factors that may cause variations in the therapeutic response to HU in cancer, sickle cell anemia, thalassemia intermedia and other groups of patients. Further studies are needed to clarify the interaction mechanisms of HU with metal ions in vitro, in vivo and in clinical conditions.