Liver and spleen sections were stained with Perls’ Prussian blue, and hepatic and splenic

iron concentrations were determined. qRT-PCR was used to assess mRNA expression. Results: Wild type and Mdr2-/- mice fed an iron deficient diet developed severe systemic anaemia evidenced by reduced haemoglobin (Hgb) (WT: 67 ± 11; Mdr2-/-: 84 ± 10 g/dL). No significant differences in haematological parameters were seen in wild type or Mdr2-/- mice following 1% carbonyl iron feeding however Mdr2-/- mice had significantly elevated serum iron levels (Mdr2-/-: 463 ± 30 Talazoparib vs WT: 252 ± 14 μg/dL). Mdr2-/- mice fed a control diet had a lower hepatic iron concentration than wild type mice (7.3 ± 1.8 vs 11.2 ± 1.8 μmol Fe/g dry wt, P = 0.08) with redistribution of stainable iron

to the reticuloendothelial NU7441 solubility dmso system. Both wild type and Mdr2-/- mice fed 1% carbonyl iron had significant hepatic iron accumulation however the degree of iron loading was greater in wild type mice (HIC: 57 ± 4 vs 23 ± 2 μmol Fe/g dry wt, P < 0.001). Perls’ Prussian blue staining indicated that iron accumulation was predominantly in reticuloendothelial macrophages in contrast to a hepatocellular distribution seen in wild types. Splenic iron concentration was similar in wild type and Mdr2-/- mice fed a control diet (38.5 ± 3.0 vs 36.7 ± 1.8 μmol Fe/g dry wt) however was significantly higher in Mdr2-/- when compared to wild type mice following 1% carbonyl iron (64.4 ± 2.0 vs 54.3 ± 2.4 μmol Fe/g dry wt). Both hepatic and splenic iron concentration were significantly

lower in wild type and Mdr2-/- mice following an iron deficient diet. Hamp1 mRNA was upregulated in both wild type and Mdr2-/- mice following 1% carbonyl iron feeding and downregulated following an iron deficient diet. Mdr2-/- had 2.8-fold higher Tfr1 expression than wild MCE公司 type mice when fed a control diet. Tfr1 was further upregulated in both wild type and Mdr2-/- mice following an iron deficient diet. Discussion/Conclusions: The reduced hepatic iron concentration, redistribution of iron to the reticuloendothelial system and resistance to hepatic iron loading when fed a 1% carbonyl iron diet suggests that hepatocyte iron uptake is impaired in Mdr2-/- mice. This work may explain the paucity of iron loading in biliary cirrhosis and suggests that iron homeostasis depends upon an appropriately functioning biliary system. 1. Stuart et al. Hepatology 2000;32(6):1200–1207. 2. Ludwig et al. Gastroenterology 1997;112:882–888.