Role of iron in inducing oxidative stress in thalassemia: can it be
prevented by inhibition of absorption and by antioxidants?
Ann N Y Acad Sci. 2005 Nov; 1054: 118-23
Rachmilewitz EA, Weizer-Stern O, Adamsky K, Amariglio N, Rechavi G,
Breda L, Rivella S, Cabantchik ZI
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.
http://www.hubmed.org/display.cgi?uids=16339657