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Biological Trace Element Research

, Volume 153, Issue 1–3, pp 243–250 | Cite as

Effects of Dietary Factors on the Pharmacokinetics of 58Fe-labeled Hemin After Oral Administration in Normal Rats and the Iron-deficient Rats

  • Yongjie Zhang
  • Di Zhao
  • Jie Xu
  • Chunxiang Xu
  • Can Dong
  • Qingwang Liu
  • Shuhua Deng
  • Jie Zhao
  • Wei Zhang
  • Xijing Chen
Article

Abstract

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 58Fe 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.

Keywords

Fe Hemin Iron-deficient rats Iron absorption Pharmacokinetics Dietary factors ICP-MS 

Abbreviations

ICP-MS

Inductively coupled plasma mass spectrometry

AUC

Area under concentration–time curve

Cmax

Maximum plasma concentration

CLz

Clearance

Vz

Apparent volume of distribution

t1/2

Half life time

MRT

Mean retention time

RBC

Erythrocyte count

Hb

Hemoglobin

Hct

Hematocrit

RDW

Red cell distribution width

MCV

Mean corpuscular volume

MCH

Mean corpuscular hemoglobin

MCHC

Mean corpuscular hemoglobin concentration

SI

Serum iron

TIBC

Total iron-binding capacity

TS

Transferrin saturation

SF

Serum ferritin

TRF

Transferritin

PCFT/HCP1

Heme carrier protein 1

DMT1

Divalent metal transporter 1

Notes

Acknowledgments

The study was supported by Jiangsu Province Nanjing City Innovative Graduate Research Program (No. CXLL11_0814) and Jiangsu Province Promotion Foundation for the Key Lab of Drug Metabolism and Pharmacokinetics (No. BM2012012).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yongjie Zhang
    • 1
  • Di Zhao
    • 1
  • Jie Xu
    • 1
  • Chunxiang Xu
    • 2
  • Can Dong
    • 2
  • Qingwang Liu
    • 3
  • Shuhua Deng
    • 1
  • Jie Zhao
    • 1
  • Wei Zhang
    • 1
  • Xijing Chen
    • 1
  1. 1.Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Jiangsu Product Quality Test & Inspect InstituteNanjingPeople’s Republic of China
  3. 3.State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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