title: Hydroxyurea could be a good clinically relevant iron chelator.
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.
authors.affiliation: Hematogenetics Department, National Institute of Immunohaematology, I.C.M.R., Mumbai, Maharashtra, India.
authors.forename: Khushnooma
authors.initials: K
authors.lastname: Italia
authors.affiliation: Hematogenetics Department, National Institute of Immunohaematology, I.C.M.R., Mumbai, Maharashtra, India.
authors.forename: Roshan
authors.initials: R
authors.lastname: Colah
authors.affiliation: National Institute of Immunohaematology, I.C.M.R., Mumbai, Maharashtra, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000986:Antisickling Agents; D005260:Female; D005290:Ferric Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D006918:Hydroxyurea / Q000493:pharmacokinetics / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D019190:Iron Overload / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000986:Antisickling Agents; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006918:Hydroxyurea