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Role of Iron in Inducing Oxidative Stress in Thalassemia: Can It Be Prevented by Inhibition of Absorption and by Antioxidants?
Author(s) -
RACHMILEWITZ ELIEZER A.,
WEIZERSTERN ORLY,
ADAMSKY KONSTANTIN,
AMARIGLIO NINETTE,
RECHAVI GIDEON,
BREDA LAURA,
RIVELLA STEFANO,
CABANTCHIK Z IOAV
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1345.014
Subject(s) - hepcidin , oxidative stress , chemistry , reactive oxygen species , thalassemia , cell , biochemistry , microbiology and biotechnology , medicine , anemia , biology
A bstract : The pathophysiology of thalassemia is, to a certain extent, associated with the generation of labile iron in the pathological red blood cell (RBC). The appearance of such forms of iron at the inner and outer cell surfaces exposes the cell to conditions whereby the labile metal promotes the formation of reactive oxygen species (ROS) leading to cumulative cell damage. Another source of iron accumulation results from increased absorption due to decreased expression of hepcidin. The presence of labile plasma iron (LPI) was carried out using fluorescent probes in the FACS. RNA expression of hepcidin was measured in two models of thalassemic mice. Hepcidin expression was also measured in human hapatoma HepG2 cells following incubation with thalassemic sera. LPI was identified and could be quantitatively measured and correlated with other parameters of iron overload. Hepcidin expression was downregulated in the livers of thalassemic mice, in major more than in intermedia. Thalassemic sera down regulated hepcidin expression in HepG2 liver cells. A possible way to decrease iron absorption could be by modulating hepcidin expression pharmacologically, by gene therapy or by its administration. Treatment with combination of antioxidants such as N ‐acetylcysteine for proteins and vitamin E for lipids in addition to iron chelators could neutralize the deleterious effects of ROS and monitored by quantitation of LPI.