Document Detail


Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox.
MedLine Citation:
PMID:  22705364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias, and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. This study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 mL/kg of RBC). We prospectively analyzed 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.
Authors:
Shohei Kikuchi; Masayoshi Kobune; Satoshi Iyama; Tsutomu Sato; Kazuyuki Murase; Yutaka Kawano; Kohichi Takada; Kaoru Ono; Yumiko Kaneko; Koji Miyanishi; Yasushi Sato; Tsuyoshi Hayashi; Rishu Takimoto; Junji Kato
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Publication Detail:
Type:  Journal Article     Date:  2012-06-15
Journal Detail:
Title:  Free radical biology & medicine     Volume:  53     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-13     Completed Date:  2012-12-21     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  643-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD
Benzoates / pharmacology,  therapeutic use*
Case-Control Studies
DNA Damage*
Deoxyguanosine / analogs & derivatives,  blood
Erythrocyte Transfusion / adverse effects*
Ferritins / blood
Genome, Human
Humans
Iron Chelating Agents / pharmacology,  therapeutic use*
Iron Overload / blood,  etiology,  prevention & control*
Leukocytes, Mononuclear / drug effects,  metabolism
Myelodysplastic Syndromes / blood,  drug therapy*
Prospective Studies
Reactive Oxygen Species / blood
Statistics, Nonparametric
Triazoles / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/Antigens, CD; 0/Benzoates; 0/Iron Chelating Agents; 0/Reactive Oxygen Species; 0/Triazoles; 9007-73-2/Ferritins; 961-07-9/Deoxyguanosine; V8G4MOF2V9/deferasirox

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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