Abstract
Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl’s Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.
Highlights
Chronic blood transfusion therapy in β-thalassemia leads to an average iron accumulation of approximately 0.3-0.5mg/kg/day [1]
A statistically and clinically significant reduction in mean serum ferritin levels (p
A statistically significant reduction (p
Summary
Chronic blood transfusion therapy in β-thalassemia leads to an average iron accumulation of approximately 0.3-0.5mg/kg/day [1]. Our earlier studies with hydroxyurea therapy showed a significant improvement in the clinical condition in 98% of sickle cell anemia patients and 60% of the β-thalassemia intermedia patients [4,5]. This was in agreement with many studies [6,7,8]. Noticed was a sharp reduction in the serum ferritin of some patients on hydroxyurea therapy without changing the chelation regimen [5,9,10] It was not possible in this clinical setup to conclusively conclude on clinically significant iron removal effect of hydroxyurea as most of the patients were on regular blood transfusion and reduction in serum ferritin in these patients could have been due to reduction in the number of blood transfusions
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