Blood Res.  2015 Sep;50(3):140-146. 10.5045/br.2015.50.3.140.

Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

Affiliations
  • 1Department of Clinical Research Laboratory, Incheon St. Mary's Hospital, Incheon, Korea.
  • 2Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea. dcjeong@catholic.ac.kr
  • 4Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 5Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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-2b/d) and a male C57/BL6 (H-2b) 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).
CONCLUSION
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.

Keyword

Iron overload; Hepatic veno-occlusive disease; Radiation; Reactive oxygen species

MeSH Terms

Alanine Transaminase
Animals
Dextrans
Female
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells*
Hepatic Veno-Occlusive Disease*
Humans
Iron Overload*
Iron*
Liver
Male
Mice*
Models, Animal
Reactive Oxygen Species
Tissue Donors
Whole-Body Irradiation
Alanine Transaminase
Dextrans
Iron
Reactive Oxygen Species
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