title: Deferasirox reduces oxidative stress in patients with transfusion dependency.
abstract: BACKGROUND
  Iron chelation therapy is useful against the over-accumulation of iron and is expected to reduce oxidative stress resulting from the Fenton reaction and Haber-Weiss reaction. We monitored oxidative status and serum ferritin levels after in vivo administration of deferasirox (DFS) and studied the in vitro effects of iron chelators on neutrophil function.
  
  
  METHODS
  Nine patients suffering from transfusion dependency were recruited for this study, and derivatives of reactive oxygen metabolite (dROM) tests to detect serum hydroperoxide levels were evaluated in addition to serum ferritin levels. Human neutrophil reactive oxygen species (ROS) production was determined with flow cytometry.
  
  
  RESULTS
  Ferritin levels decreased after DFS treatment (P = 0.068), and a significant reduction in dROM levels was measured (P = 0.031). Fifty microM DFS significantly inhibited ROS production induced by fMLP in vitro (P < 0.0001), and tended to inhibit that induced by PMA. On the other hand, deferioxamine failed to inhibit ROS production even at high concentrations.
  
  
  CONCLUSIONS
  In vivo administration of DFS resulted in the reduction of oxidative stress, and this effect was considered to depend not only on a reduction in iron storage but also on the ability of DFS to inhibit neutrophil ROS production in vitro at clinically relevant plasma levels. Further studies are needed to examine the effects of iron chelators.
authors: Faculty of Pharmacological Sciences, Himeji Dokkyo University, 7-Kami-ohno, Himeji, Hyogo, Japan.
authors: Katsuyasu
authors: K
authors: Saigo
authors: Mari
authors: M
authors: Kono
authors: Yuri
authors: Y
authors: Takagi
authors: Mariko
authors: M
authors: Takenokuchi
authors: Yasushi
authors: Y
authors: Hiramatsu
authors: Hiroshi
authors: H
authors: Tada
authors: Terutoshi
authors: T
authors: Hishita
authors: Masahito
authors: M
authors: Misawa
authors: Shion
authors: S
authors: Imoto
authors: Shinsaku
authors: S
authors: Imashuku
keywords: Deferasirox; Ferritin; Neutrophil; Oxidative stress; dROM
references: Blood Transfus. 2013 Jan;11(1):53-60
references: 22790260
references: Free Radic Biol Med. 2012 Aug 15;53(4):643-8
references: 22705364
references: N Engl J Med. 2011 Jan 13;364(2):146-56
references: 21226580
references: Acta Med Okayama. 2010 Oct;64(5):323-30
references: 20975766
references: J Clin Lab Anal. 2009;23(5):319-23
references: 19774625
references: J Clin Oncol. 2007 Aug 10;25(23):3503-10
references: 17687155
references: Haematologica. 2008 Jun;93(6):817-25
references: 18469351
references: Transfusion. 2010 Jul;50(7):1568-70
references: 20230535
references: Biochem Biophys Res Commun. 2007 Apr 27;356(1):312-7
references: 17349976
references: Haematologica. 2010 Aug;95(8):1433-4
references: 20421274
references: J Clin Med Res. 2012 Feb;4(1):52-5
references: 22383928
references: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1331-8
references: 15498822
references: Transfus Apher Sci. 2005 Nov;33(3):289-98
references: 16199204
references: J Int Med Res. 2011;39(5):1941-5
references: 22117997
references: Free Radic Biol Med. 2009 Jul 1;47(1):62-71
references: 19376220
references: Haematologica. 2010 Aug;95(8):1308-16
references: 20534700
references: Blood. 2006 Nov 1;108(9):3195-203
references: 16835377
references: Shock. 2007 Aug;28(2):154-9
references: 17529906
references: Acta Haematol. 2011;126(4):241-5
references: 21951998