Musumeci Marco, Maccari Sonia, Massimi Alessia, Stati Tonino, Sestili Paola, Corritore Elisa, Pastorelli Augusto, Stacchini Paolo, Marano Giuseppe, Catalano Liviana
Pharmacology Department, Health and Food Safety, National Institute of Health, Rome, Italy.
Cellular Biology Department, Health and Food Safety, National Institute of Health, Rome, Italy.
Blood Transfus. 2014 Oct;12(4):485-90. doi: 10.2450/2014.0288-13. Epub 2014 Jun 5.
Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained.
Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration.
In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time.
This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion.
人体中的铁稳态由旨在保存铁以供再利用的机制严格调控，排泄机制所起的作用微不足道。在先前的一项研究中，我们发现小鼠具有惊人的能力，能够耐受非常高剂量的肠胃外给予的右旋糖酐铁。这种能力是否与排泄途径的存在有关仍有待确定。
通过在两种不同的小鼠品系（C57bl/6和B6D2F1）中每周腹腔注射一次右旋糖酐铁（1 g/kg），持续8周来产生铁过载。通过电感耦合等离子体质谱法评估尿和粪便中的铁排泄，而通过超声心动图和组织学方法评估心脏和肝脏结构。对于这两个品系，在给予铁后的第0、1和2天收集24小时的粪便和尿液样本，并测定铁浓度。
在铁过载的C57bl/6小鼠中，粪便铁浓度在第1天和第2天分别增加了218%和157%（p<0.01）。排泄出的铁占给予的总铁量的14%。在B6D2F1小鼠中也发现了类似但较小的变化。相反，我们在这两种品系的小鼠尿液中铁浓度均未发现显著变化。在这两个品系中，组织学检查均显示肝脏和心脏中有铁蓄积，且这种蓄积倾向于随时间减少。
本研究表明小鼠具有清除体内多余铁的机制，并为可能的排泄机制提供了见解。
