title: Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation.
abstract: BACKGROUND
  The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT.
  
  
  METHODS
  We used a 6-week-old female BDF1 (H-2(b/d)) and a male C57/BL6 (H-2(b)) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings.
  
  
  RESULTS
  ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01).
  
  
  CONCLUSIONS
  Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation.
authors.affiliation: Department of Clinical Research Laboratory, Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Yeom
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nack Gyun
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Pil Sang
authors.initials: PS
authors.lastname: Jang
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul Seung
authors.initials: CS
authors.lastname: Kye
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea. ; Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dae Chul
authors.initials: DC
authors.lastname: Jeong
keywords: Hepatic veno-occlusive disease; Iron overload; Radiation; Reactive oxygen species