Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 Jiangsu, People's Republic of China.
Biol Trace Elem Res. 2013 Jun;153(1-3):243-50. doi: 10.1007/s12011-013-9654-3. Epub 2013 Apr 13.
Hemin, iron (III) protoporphyrin chloride (IX), as a stable form of heme iron, has been used in iron absorption studies. The aim of the present study was to elucidate the influences of body iron status and three dietary factors (green tea extract, ascorbic acid, and calcium) on the pharmacokinetics of hemin using stable isotope labeling methods followed by ICP-MS measurement. In this study, a rapid, sensitive, and specific ICP-MS method for the determination of (58)Fe originating from hemin in rat plasma was developed and a rat model of iron deficiency anemia was established. It was found that hemin iron absorption increased significantly under iron deficiency anemia status, with AUC0-t and AUC0-∞ showing significant increase in anemic rats compared to normal ones. Green tea extract strongly inhibited hemin iron absorption in both normal rats and iron-deficient rats. In normal rats administered with green tea extract, C max resulted significantly reduced, whereas in anemic rats administered with green tea extract both AUC0-t and AUC0-∞ were reduced. On the other hand, ascorbic acid significantly affected hemin iron absorption only in iron-deficient rats, in which C max showed a significant increase. Interestingly, calcium slowed down the hemin iron absorption rate in normal rats, MRT0-t being significantly different in calcium-treated animals compared to untreated ones. This trend also appeared in the iron-deficient group but it did not reach statistical significance. Our data suggest that the mechanism of hemin iron absorption is regulated by body iron status and dietary factors can influence hemin iron absorption to varying degrees. Moreover, these results may also have general implication in the iron deficiency treatment with iron supplements and fortification of foods.
血晶素，三价氯化原卟啉铁（IX），作为血红素铁的稳定形式，已被用于铁吸收研究。本研究旨在阐明机体铁状态和三种膳食因素（绿茶提取物、抗坏血酸和钙）对血晶素药代动力学的影响，方法是采用稳定同位素标记法，随后用 ICP-MS 进行测量。在这项研究中，建立了一种快速、灵敏、特异的 ICP-MS 方法，用于测定大鼠血浆中源自血晶素的（58）Fe。同时建立了缺铁性贫血大鼠模型。结果发现，在缺铁性贫血状态下，血晶素铁的吸收显著增加，与正常大鼠相比，贫血大鼠的 AUC0-t 和 AUC0-∞均显著增加。绿茶提取物在正常大鼠和缺铁大鼠中均强烈抑制血晶素铁的吸收。在给予绿茶提取物的正常大鼠中，Cmax 显著降低，而在给予绿茶提取物的贫血大鼠中，AUC0-t 和 AUC0-∞均降低。另一方面，抗坏血酸仅在缺铁大鼠中显著影响血晶素铁的吸收，Cmax 显著增加。有趣的是，钙在正常大鼠中减缓了血晶素铁的吸收速度，MRT0-t 在钙处理动物中与未处理动物有显著差异。这种趋势在缺铁组中也出现，但没有达到统计学意义。我们的数据表明，血晶素铁的吸收机制受机体铁状态的调节，膳食因素可以在不同程度上影响血晶素铁的吸收。此外，这些结果可能对缺铁症的铁补充治疗和食物强化具有普遍意义。
