Levine D S, Huebers H A, Rubin C E, Finch C A
Department of Medicine, University of Washington, Seattle.
Gastroenterology. 1988 Nov;95(5):1242-8. doi: 10.1016/0016-5085(88)90357-5.
Desferrioxamine (DFO) is an iron chelating agent that, when administered orally, interferes with gut absorption of inorganic iron and, when administered parenterally, binds body iron and is excreted as ferrioxamine in bile and urine. Studies were carried out in normal and iron-deficient male rats and in normal, iron-replete male volunteers to investigate the blocking action of parenteral DFO on the absorption of radioiron. Radiolabeled ferrous ammonium sulfate, transferrin iron, or hemoglobin iron was injected directly into the jejunum of rats with or without intramuscular injections of DFO. Radioiron administered as ferrous sulfate or as transferrin iron was given to the volunteers by mouth or by direct duodenal infusion, respectively, with or without intravenous infusions of DFO. In iron-deficient rats, intramuscular DFO injections commencing 1 h before direct jejunal injection of radioiron significantly blocked absorption of inorganic iron (26% with DFO, 64% without DFO), transferrin iron (4% with DFO, 69% without DFO), and hemoglobin iron (3% with DFO, 19% without DFO). In normal rats, DFO injections also significantly blocked absorption of inorganic iron and transferrin iron. In normal volunteers, intravenous DFO infusions commencing 1 h before administration of radioiron significantly blocked absorption of physiologic doses of inorganic iron (3% with DFO, 21% without DFO) and transferrin iron (1% with DFO, 20% without DFO). The quantity of radioiron excreted in urine by both rats and humans with administration of DFO did not account for the observed decrement in absorption of radioiron. Biochemical analysis of rat intestinal mucosal scrapings after injection of DFO and administration of radioiron demonstrated the accumulation of a small molecular weight fraction containing iron that was ferrioxamine (iron-chelate) complex. We conclude that parenterally administered DFO can enter the small intestinal mucosa, bind intracellular iron, and block iron absorption. Parenteral DFO blocks the absorption of inorganic iron, transferrin iron, and hemoglobin iron, suggesting that all three iron species enter a common chelatable pool within the small intestinal mucosa and may share a common pathway of absorption.
去铁胺（DFO）是一种铁螯合剂，口服时会干扰肠道对无机铁的吸收，胃肠外给药时会结合体内铁，并以铁胺的形式经胆汁和尿液排出。在正常和缺铁雄性大鼠以及正常、铁充足的雄性志愿者身上开展了研究，以调查胃肠外给予DFO对放射性铁吸收的阻断作用。将放射性标记的硫酸亚铁铵、转铁蛋白铁或血红蛋白铁直接注入接受或未接受肌肉注射DFO的大鼠空肠。分别通过口服或直接十二指肠输注的方式，将作为硫酸亚铁或转铁蛋白铁给予志愿者的放射性铁，同时接受或不接受静脉输注DFO。在缺铁大鼠中，在直接空肠注射放射性铁前1小时开始肌肉注射DFO，可显著阻断无机铁（DFO组为26%，未用DFO组为64%）、转铁蛋白铁（DFO组为4%，未用DFO组为69%）和血红蛋白铁（DFO组为3%，未用DFO组为19%）的吸收。在正常大鼠中，注射DFO也显著阻断了无机铁和转铁蛋白铁的吸收。在正常志愿者中，在给予放射性铁前1小时开始静脉输注DFO，可显著阻断生理剂量的无机铁（DFO组为3%，未用DFO组为21%）和转铁蛋白铁（DFO组为1%，未用DFO组为20%）的吸收。给予DFO后，大鼠和人类尿液中排出的放射性铁量无法解释观察到的放射性铁吸收减少情况。对注射DFO并给予放射性铁后的大鼠肠黏膜刮片进行生化分析，结果显示积累了一小部分含有铁的小分子物质，即铁胺（铁螯合物）复合物。我们得出结论，胃肠外给予的DFO可进入小肠黏膜，结合细胞内铁，并阻断铁吸收。胃肠外给予的DFO可阻断无机铁、转铁蛋白铁和血红蛋白铁的吸收，这表明这三种铁形式均进入小肠黏膜内一个共同的可螯合池，并可能共享一条共同的吸收途径。
