In vitro assessment of deferoxamine on mesenchymal stromal cells from tumor and bone marrow

Deferoxamine (DFO), an iron chelator, is commonly used to remove excess iron from the body. DFO has also been demonstrated to have anti-tumor effect. However, there is no available report on the effect of deferoxamine on mesenchymal stromal cells (MSCs). In this study, we first isolated tumor-associated MSCs (TAMSCs) from EG-7 tumors, which were positive for CD29, CD44, CD73, CD90 and CD105. Ex vivo cultured stem cells derived from tumor and bone marrow compartment were exposed to DFO. We demonstrated that DFO had growth-arresting and apoptosis-inducing effect on TAMSCs and bone marrow MSCs (BMMSCs). DFO also influenced the expression pattern of adhesion molecule VCAM-1 on both TAMSCs and BMMSCs. Notwithstanding its widespread use, our results here warrants caution in the application of DFO, and also highlights the need for careful evaluation of the bone marrow compartment in patients receiving DFO treatment.     

Identification of the Asymmetric Hybrid of Human Oxy Hemoglobins A and S (α2βAβS) at 4° C by Cellulose Acetate Electrophoresis

Millions of people are affected by hereditary hemochromatosis (HH) and thalassemia intermedia (TI), the iron overloading disorders caused by chronic increases in iron absorption. Genetic factors, regulatory pathways involving proteins of iron metabolism, non regulatory molecules, dietary constituents and iron binding drugs could affect iron absorption and could lead to iron overload or iron deficiency. Chelators and chelating drugs can affect both iron absorption and excretion. Deferoxamine (DFO), deferiprone (L1) and the DFO/L1 combination therapies have been used effectively for reversing the toxic side effects of iron overload including cardiac and liver damage in TI and HH patients where venesection is contraindicated. Selected protocols using DFO, L1 and their combination could be designed for optimizing chelation therapy in TI and HH. The use of deferasirox (DFRA) in HH and TI could cause an increase in iron and other toxic metal absorption. Future treatments of HH and TI could involve the use of iron chelating and other drugs not only for increasing iron excretion but also for preventing iron absorption.     

Thalassemia Incidence and Treatment in China with Special Reference to Shenzhen City and Guangdong Province

According to the data from different screening studies, thalassemia is the most commonly seen hereditary hemolytic disease in China. The reported prevalence of thalassemia carriers varies but it is most prevalent in Southern China. In the past, the outcome of patients with thalassemia major has been very poor due to unfavorable economic background. With economic improvement in the past 10 years, increasing number of patients can get regular transfusion and chelation, and more patients can be treated by hemopoietic stem cell transplantation. A better prevention network has been built up over the years, but there are still babies being born with severe forms of thalassemia every year. A more comprehensive preventive program and public education are vital.     

To chelate or not to chelate in MDS: That is the question!

Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions.     

Intranasal deferoxamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer's disease

Increasing evidence indicates that a disturbance of normal iron homeostasis and an amyloid-β (Aβ)-iron interaction may contribute to the pathology of Alzheimer's disease (AD), whereas iron chelation could be an effective therapeutic intervention. In the present study, transgenic mice expressing amyloid precursor protein (APP) and presenilin 1 and watered with high-dose iron served as a model of AD. We evaluated the effects of intranasal administration of the high-affinity iron chelator deferoxamine (DFO) on Aβ neuropathology and spatial learning and memory deficits created in this AD model. The effects of Fe, DFO, and combined treatments were also evaluated in vitro using SHSY-5Y cells overexpressing the human APP Swedish mutation. In vivo, no significant differences in the brain concentrations of iron, copper, or zinc were found among the treatment groups. We found that high-dose iron (deionized water containing 10 mg/mL FeCl₃) administered to transgenic mice increased protein expression and phosphorylation of APP695, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory. Chelation of iron via intranasal administration of DFO (200 mg/kg once every other day for 90 days) inhibited iron-induced amyloidogenic APP processing and reversed behavioral alterations. DFO treatment reduced the expression and phosphorylation of APP protein by shifting the processing of APP to the nonamyloidogenic pathway, and the reduction was accompanied by attenuating the Aβ burden, and then significantly promoted memory retention in APP/PS1 mice. The effects of DFO on iron-induced amyloidogenic APP cleavage were further confirmed in vitro. Collectively, the present data suggest that intranasal DFO treatment may be useful in AD, and amelioration of iron homeostasis is a potential strategy for prevention and treatment of this disease.     

Effects of Deferoxamine on the Repair Ability of Dental Pulp Cells In Vitro

Introduction

In previous studies, we found that hypoxia promoted the mineralization of dental pulp cells (DPCs). However, the clinical application of hypoxia as a therapy is questionable or unfeasible. Deferoxamine (DFO), a medication for iron overload, has also been shown to induce hypoxia. The purpose of this study was to investigate the effects of DFO on the repair ability of DPCs.

Methods

DPCs were obtained by using a tissue explant technique in vitro and were treated with different concentrations of DFO or hypoxia culture for 2 days. The viability, proliferation, migration, and odontogenic differentiation of DPCs were assayed and analyzed. The expression of hypoxia-inducible factor 1-alpha (HIF-1α) was assessed through Western blotting.

Results

Ten micromolars of DFO enhanced the expression of HIF-1α similarly to hypoxia and did not affect the viability of DPCs for 2 days. Furthermore, the proliferation, migration, and odontogenic differentiation of DPCs were promoted by DFO.

Conclusions

These results suggest that DFO might improve the repair ability of DPCs by HIF-1α.     

大鼠脊髓损伤后含铁血黄素的变化及去铁敏的研究

目的初步探讨含铁血黄素在大鼠脊髓损伤后的变化及去铁敏的干预作用。方法健康成年雄性SD大鼠90只,随机分为正常组10只、损伤不治疗组40(只)及去铁敏治疗组40(只)。大鼠急性脊髓损伤模型制作采用改良Allen’s法,于伤后1 d、7 d、14 d、28 d、56 d在脊髓损伤部位取材,行病理学(HE染色、和Perl’s普鲁士蓝)检查。通过运动功能评分法(BBB)观察每组动物给药前后不同时间点的神经功能改善情况。结果病理结果:①HE染色:去铁敏治疗组较正常损伤组:7 d后发现残存神经元数量较正常损伤明显增多,损伤周围胶质细胞增生明显,Nissl体较正常损伤组明显增多;14 d时,上述表现较7 d时更加明显;②Perl’s染色:损伤后1 d在去铁敏治疗组和损伤组没有发现含铁血黄素细胞,7 d后去铁敏治疗组损伤区含铁血黄素较同期损伤组明显增多,14 d后去铁敏治疗组含铁血黄素明显少于同期损伤组;28 d和56 d时,含铁血黄素无明显区别,均明显的减少。神经功能改善情况:术后24 h治疗组和对照组无明显的差异(P>0.05),7 d时治疗组明显好于对照组(P<0.01),14 d,28 d,56 d均明显优于对照组(P<0.01)。结论去铁敏对大鼠脊髓损伤后神经功能的改善有明显的效果。     

脑出血后铁代谢异常

脑出血(intracerebral hemorrhage, ICH)是一种临床常见的高致残率和高死亡率的脑血管病.大量临床和实验研究表明,ICH后血肿周围脑组织铁代谢异常是造成脑水肿和神经细胞凋亡等继发性脑损伤的重要原因,是影响患者转归的重要因素.文章对ICH后铁代谢异常及其意义进行了综述.