Iron is an essential trace element for normal functions of the body. Restriction of iron availability directly limits erythropoiesis. The objective of this experiment was to compare the bioavailability of iron nanoparticles (Fe-NPs) with iron-microparticles (Fe-MPs) in anemic mice. There were four experimental groups, including the normal control group, iron-deficiency anemia (IDA) group, Fe-NPs group, and Fe-MPs group. Animals in the normal group fed on an adequate iron-containing diet (45 ppm Fe). Meanwhile, animals in the other three groups fed on a low Fe diet (4.5 ppm Fe) for seven weeks. Double deionized water was supplied as drinking water ad libitum. After feeding for three weeks with the low Fe diet, animals in the Fe-NPs and Fe-MPs groups received oral administration of Fe-NPs or Fe-MPs at a daily dose of 40 mg/kg for four weeks. The IDA group showed markedly decreased red blood cell (RBC) count, hematocrit (Hct), and hemoglobin (Hb) values compared with the normal group throughout the experimental periods. Treatments with Fe-NPs or Fe-MPs for four weeks resulted in restoration of the decreased RBC count and hematological values similar to normal values. The Fe-NPs group showed faster restoration in values than Fe-MPs with passage of time. The iron contents of the upper small intestine in the Fe-NPs and Fe-MPs groups were higher than in the normal group at weeks 2 and 4. Treatment with Fe-NPs and Fe-MPs resulted in a significant increase in hepatic iron contents and lipid peroxidation, compared with the IDA group with passage of time. The iron contents in liver and ferritin deposits in spleen were identified in the Fe-NPs and Fe-MPs groups, similar to the normal group. These results indicate that oral administration of both Fe-NPs and Fe-MPs can result in recovery from anemia and Fe-NPs is more absorbable and available in the body than Fe-MPs.

Epigenetic modification dependent DNA methyltransferases (DNMTs) play an important role in tissue- and stage-specific gene regulation and normal mammalian development. In this study, we show that DNMTs are expressed at different levels during hematopoietic stem cell (HSC) differentiation to proerythrocytes. DNMT1, DNMT3A, and DNMT3B were highly expressed at day 7 after differentiation. We used specific siRNA as a tool to probe the relationship between the expression of DNMTs and erythropoietic differentiation. When introduced siRNA of DMNT1 and DMNT3b in human CD34+ cells, these more differentiated into erythrocytes. This was confirmed by glycophorin A (GPA) positive cell analysis and globin gene expression. GPA+ cells increased up to 20～30%, and γ- and ε-globin genes increased in siRNA transfected cells. Therefore, our data suggest that suppression of DNA methylation can affect positively differentiation of HSC and may contribute to expression of erythrocyte lineage genes including GPA and globins.