A Randomized Prospective Study to Assess the Effect of Vitamin E on Peroxiredoxin- 2 As a Novel Antioxidant Marker in Young Beta-Thalassemia Major Patients on Different Chelation Therapy

Introduction: Oxidative stress plays a central role in the pathogenesis of morbidities in β-thalassemia. Peroxiredoxin-2 (PRDX2) is the third most abundant cytoplasmic protein in red cells and is able to reduce and detoxify a vast range of organic peroxides, H2O2, and peroxynitrite. PRDX2 has been demonstrated to be induced by oxidative stress and that cells overexpressing PRDX2 are more resistant to the oxidative stress. Vitamin E is a fat-soluble vitamin and an anti-oxidant which is often depleted in thalassemia patients as a result of iron overload. Aim: This randomized prospective trial aimed to investigate the efficacy and safety of vitamin E as an adjuvant therapy to the three used iron chelators in moderately iron overloaded young vitamin E-deficient β-thalassemia major (β-TM) patients in relation to tissue iron overload and examine its potential corrective value to markers of oxidative stress and to the level of PRDX2 as a novel protective marker of oxidative stress. Methods: Inclusion criteria were β-TM patients aged 6-18 years, vitamin E deficient, serum ferritin (SF) >1000-2500 μg/L and cardiac T2* > 10 ms and ejection fraction > 56 %. A total of 245 β-TM patients were screened for eligibility, 180 were enrolled while 35 did not meet inclusion criteria and 30 were excluded. The 180 β-TM vitamin E-deficient patients were equally enrolled into 3 groups (each; n=60) and received desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin E supplementation (400 IU daily) or not (n=30). All patients received vitamin E (group A) or no vitamin E (group B) were followed-up for one year with assessment of transfusion index, hemoglobin, serum ferritin (SF), liver iron content (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Malondialdehyde (MDA), as an index for lipid peroxidation, and antioxidants including reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase and PRXD2 were assessed. Results: Baseline vitamin E was negatively correlated to SF, LIC and MDA while it was positively correlated to GSH, GPX, catalase and PRXD2. No significant difference was found as regards the studied variables at baseline and study end in patients who did not receive vitamin E (group B). After vitamin E therapy, transfusion index, SF, and LIC were significantly decreased in group A patients while hemoglobin and cardiac MRI T2* were elevated compared wi