title: [In vitro effect of iron overload on bone marrow cell function by inducing the reactive oxygen species].
abstract: OBJECTIVE
  To investigate the in vitro effect of iron overload on the generation of reactive oxygen species (ROS) and of bone marrow (BM) cell function.
  
  
  METHODS
  BM mononuclear cells (BMMNCs) were cultured with ferric citrate (FAC) at different concentrations and for different time to create iron overload and confirmed by the detection of cellular labile iron pool (LIP). The changes of ROS, apoptosis, hematopoietic colony formation (CFU-E, BFU-E, CFU-GM and CFU-mix) and the percentage of the CD34 + cells percentage were analyzed. The differences of these index were tested after the iron overload treated with deferasirox (DFO) or antioxidants (N-acetyl-L-cysteine, NAC).
  
  
  RESULTS
  1) When BMMNCs were cultured with FAC, the LIP was found to increase in a time and concentration dependent manner. The intracellular LIP reached maximum at 400 micromol/L of FAC for 24 hours. 2) The ROS of total cells, leukocytes and erythrocytes increased to 1.77, 1.75 and 2.12 fold respectively compared with that of normal control when cells were cultured at 400 micromol/L of FAC for 24 hours . DFO and NAC could reduce the ROS efficiently (P<0.05). 3) The apoptotic rates of the FAC treated cells [(24.80 +/- 2.99)%] increased significantly compared with that of normal control [(8.90 +/- 0.96)%]. The capacity of hematopoietic colony formation in FAC treated cells decreased markedly compared with that of normal control (P<0.05). The percentage of CD34+ cells of FAC treated cells [(0.39 +/- 0.07)%] also decreased significantly compared with that of normal control [(0.91 +/- 0.12)%]. And these changes could be recovered by addition of NAC or DFO.
  
  
  CONCLUSIONS
  Iron overload can affect the hematopoiesis by inducing the generation of ROS and this damage could be corrected by removing the excess iron and ROS of the BM cells. These findings might improve the treatment of dyshematopoiesis in patients with iron overload.
authors.affiliation: Tianjin First Central Hospital, Tianjin Medical University, Tianjin 300192, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Ming-feng
authors.initials: MF
authors.lastname: Zhao
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Li
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xin-nü
authors.initials: XN
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.forename: Juan
authors.initials: J
authors.lastname: Mu
authors.forename: Peng-jiang
authors.initials: PJ
authors.lastname: Liu
authors.forename: Hai-rong
authors.initials: HR
authors.lastname: Lü
mesh_terms: D001854:Bone Marrow Cells / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004912:Erythrocytes; D005290:Ferric Compounds / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D019190:Iron Overload; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D003470:Culture Media; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C025314:ferric citrate