A composite mouse model of aplastic anemia complicated with iron overload

Abstract

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

The effect of iron dextran on vitamin D3 metabolism in SD rats

“…Our study found that iron deficiency reduced the iron concentration in the liver and kidney, the SI concentration was increased accordingly, the SI concentration in HFe group is lower than that in LFe group and MFe group, which is consistent with the study obtained by DiJiong et al [ 25 ]. In this study, the down-regulation of the expression of CYP2R1 and CYP27A1 at the protein and gene levels, the up-regulation of the expression of CYP27B1 and the expression of VD catabolic enzyme CYP24A1 was down-regulated accordingly.…”

Comparison of the effects of deferasirox, deferoxamine, and combination of deferasirox and deferoxamine on an aplastic anemia mouse model complicated with iron overload

“…The duplication of AA model complicated with iron overload was done according to our previous research. 15 Briefly, Balb/C mice were first administered with iron dextran (200 mg/kg/wk, continue for 10 weeks) via intraperitoneal injection. After establishing the iron overload model, all the mice were treated with whole-body irradiation ( 60 Co 6.0 Gy at 1 Gy/min), following administration of 0.2 mL (5×10 6 cells/mL) prepared thymus cell suspensions from DBA/2 mice; the injection was preformed via the caudal vein within 4 h.…”

“…Whether the combination treatment exerts a superior effect in iron deposition reduction and hematopoiesis recovery than the monotherapy remains unclear. In the present study, we compared the combination effect of iron chelation with DFX and DFO on an AA animal model complicated with iron overload, which was established by our group previously, 15 as well as their effect on hematopoietic recovery, to clarify the underlying mechanisms.…”

Baicalein Attenuates Brain Iron Accumulation through Protecting Aconitase 1 from Oxidative Stress in Rotenone-Induced Parkinson’s Disease in Rats

“…Baicalein demonstrates various biological activities and improves motor and non-motor symptoms in PD [19][20][21][22][23][24][25][26]. Baicalein has also been reported to chelate iron and alleviate iron accumulation [27,28]. Baicalein is well tolerated and shows little toxicity in humans [29].…”