Paesano Rosalba, Pietropaoli Miriam, Gessani Sandra, Valenti Piera
Department of Obstetrician and Gynecology, Sapienza, University of Rome, Rome, Italy.
Biochimie. 2009 Jan;91(1):44-51. doi: 10.1016/j.biochi.2008.06.004. Epub 2008 Jun 14.
Iron is a fundamental element for humans as it represents an essential component of many proteins and enzymes. However, this element can also be toxic when present in excess because of its ability to generate reactive oxygen species. This dual nature imposes a tight regulation of iron concentration in the body. In humans, systemic iron homeostasis is mainly regulated at the level of intestinal absorption and, until now, no regulated pathways for the excretion of iron have been found. The regulation and maintenance of systemic iron homeostasis is critical to human health. Excessive iron absorption leads to iron-overload in parenchyma, while low iron absorption leads to plasma iron deficiency, which manifests as hypoferremia (iron deficiency, ID) and ID anaemia (IDA). ID and IDA are still a major health problem in pregnant women. To cure ID and IDA, iron supplements are routinely prescribed. The preferred treatment of ID/IDA, consisting in oral administration of iron as ferrous sulphate, often fails to exert significant effects on hypoferremia and may also cause adverse effects. Lactoferrin (Lf), an iron-binding glycoprotein abundantly found in exocrine secretions of mammals, is emerging as an important regulator of systemic iron homeostasis. Recent data suggest that this natural compound, capable of interacting with the most important components of iron homeostasis, may represent a valuable alternative to iron supplements in the prevention and cure of pregnancy-associated ID and IDA. In this review, recent advances in the molecular circuits involved in the complex cellular and systemic iron homeostasis will be summarised. The role of Lf in curing ID and IDA in pregnancy and in the maintenance of iron homeostasis will also be discussed. Understanding these mechanisms will provide the rationale for the development of novel therapeutic alternatives to ferrous sulphate oral administration in the prevention and cure of ID and IDA.
铁是人类的一种基本元素，因为它是许多蛋白质和酶的重要组成部分。然而，由于这种元素能够产生活性氧，当其过量存在时也可能具有毒性。这种双重特性使得人体对铁浓度进行严格调控。在人类中，全身铁稳态主要在肠道吸收水平进行调节，到目前为止，尚未发现铁排泄的调控途径。全身铁稳态的调节和维持对人类健康至关重要。铁吸收过多会导致实质器官铁过载，而铁吸收过少会导致血浆铁缺乏，表现为低铁血症（缺铁，ID）和缺铁性贫血（IDA）。ID和IDA仍然是孕妇面临的主要健康问题。为了治疗ID和IDA，通常会开铁补充剂。ID/IDA的首选治疗方法是口服硫酸亚铁形式的铁，但往往对低铁血症没有显著效果，还可能引起不良反应。乳铁蛋白（Lf）是一种在哺乳动物外分泌分泌物中大量存在的铁结合糖蛋白，正成为全身铁稳态的重要调节因子。最近的数据表明，这种能够与铁稳态最重要成分相互作用的天然化合物，可能是预防和治疗妊娠相关ID和IDA中铁补充剂的有价值替代品。在这篇综述中，将总结参与复杂细胞和全身铁稳态的分子途径的最新进展。还将讨论Lf在治疗妊娠ID和IDA以及维持铁稳态中的作用。了解这些机制将为开发新型治疗方法提供理论依据，以替代口服硫酸亚铁预防和治疗ID和IDA。
