Objective: The aim of this investigation was to study the effect of vitamin E treatment in oxidative stress of red and white cells of β-thalassaemia intermedia patients. Methods: Nine patients undergoing occasional transfusions (5 females/4 males), median age 39 years (range 15–74), were recruited for oral daily administration of 400 IU vitamin E for 3 months. Twenty-seven milliliters of peripheral blood was obtained before and after 3 months of treatment, and 3 months after treatment completion. In the case of transfused patients (n = 4), blood was obtained at least 30 days after transfusion. Reactive oxygen species (ROS) was measured by flow cytometry; red blood cell (RBC) reduced glutathione (GSH) was measured by dinitrothiocyanobenzene reduction, serum malondialdehyde was measured in terms of thiobarbituric acid-reactive substances (TBARS), and α-haemoglobin-stabilizing protein (AHSP) mRNA expression was measured by real-time polymerase chain reaction of reticulocyte RNA extracts. Results: β-Thalassaemia patients presented basal levels of RBC ROS, GSH and serum TBARS statistically different compared with healthy controls. However, after vitamin E administration, patients presented a significant reduction in erythrocyte RBC ROS and serum TBARS levels. In parallel, red cell GSH was significantly increased after treatment. Peripheral mononuclear cells and T lymphocytes also demonstrated a reduction in ROS production. Therefore, after treatment, no significant differences were detected comparing patients and normal controls. Three months after treatment completion, all measurements showed a tendency of returning to basal values. A significant reduction in reticulocyte number was observed after vitamin E treatment. Vitamin E treatment did not modify levels of haemoglobin or AHSP mRNA expression. Conclusion: Although vitamin E is not capable of reducing anaemia in these patients, it could be useful for reducing oxidative damage in other target organs of β-thalassaemic patients. Finally, this is the first study to analyse the effects of vitamin E on ROS production in red and white blood cells and AHSP mRNA expression.

1.
Aessopos A, Kati M, Meletis J: Thalassemia intermedia today: should patients regularly receive transfusions? Transfusion 2007;47:792–800.
2.
Olivieri NF: The beta-thalassemias. N Engl J Med 1999;341:99–109.
3.
Clarke GM, Higgins TN: Laboratory investigation of hemoglobinopathies and thalassemias: review and update. Clin Chem 2000;46:1284–1290.
4.
Dhaliwal G, Cornett PA, Tierney LM Jr: Hemolytic anemia. Am Fam Physician 2004;69:2599–2606.
5.
Advani R, Sorenson S, Shinar E, Lande W, Rachmilewitz E, Schrier SL: Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia. Blood 1992;79:1058–1063.
6.
Scott MD, Eaton JW: Thalassaemic erythrocytes: cellular suicide arising from iron and glutathione-dependent oxidation reactions? Br J Haematol 1995;91:811–819.
7.
Yu X, Kong Y, Dore LC, Abdulmalik O, Katein AM, Zhou S, Choi JK, Gell D, Mackay JP, Gow AJ, Weiss MJ: An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis. J Clin Invest 2007;117:1856–1865.
8.
Kihm AJ, Kong Y, Hong W, Russell JE, Rouda S, Adachi K, Simon MC, Blobel GA, Weiss MJ: An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature 2002;417:758–763.
9.
Amer J, Goldfarb A, Fibach E: Flow cytometric measurement of reactive oxygen species production by normal and thalassaemic red blood cells. Eur J Haematol 2003;70:84–90.
10.
Borgna-Pignatti C: Modern treatment of thalassaemia intermedia. Br J Haematol 2007;138:291–304.
11.
Rund D, Rachmilewitz E: New trends in the treatment of beta-thalassemia. Crit Rev Oncol Hematol 2000;33:105–118.
12.
Tesoriere L, D’Arpa D, Maggio A, Giaccone V, Pedone E, Livrea MA: Oxidation resistance of LDL is correlated with vitamin E status in beta-thalassemia intermedia. Atherosclerosis 1998;137:429–435.
13.
Dhawan V, Kumar Kh R, Marwaha RK, Ganguly NK: Antioxidant status in children with homozygous thalassemia. Indian Pediatr 2005;42:1141–1145.
14.
Das N, Das Chowdhury T, Chattopadhyay A, Datta AG: Attenuation of oxidative stress-induced changes in thalassemic erythrocytes by vitamin E. Pol J Pharmacol 2004;56:85–96.
15.
Amer J, Fibach E: Chronic oxidative stress reduces the respiratory burst response of neutrophils from beta-thalassaemia patients. Br J Haematol 2005;129:435–441.
16.
Amer J, Ghoti H, Rachmilewitz E, Koren A, Levin C, Fibach E: Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol 2006;132:108–113.
17.
Gaetke LM, Chow CK: Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 2003;189:147–163.
18.
Karadag F, Cildag O, Altinisik M, Kozaci LD, Kiter G, Altun C: Trace elements as a component of oxidative stress in COPD. Respirology 2004;9:33–37.
19.
Beutler E: Reduced glutatione (GSH); in Beutler E (ed): Red Cell Metabolism: A Manual of Biochemical Methods, ed 2. New York, Grune and Stratton, 1971, pp 112–114.
20.
Amer J, Goldfarb A, Fibach E: Flow cytometric analysis of the oxidative status of normal and thalassemic red blood cells. Cytometry A 2004;60:73–80.
21.
Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR: Complications of beta-thalassemia major in North America. Blood 2004;104:34–39.
22.
Bank A: AHSP: a novel hemoglobin helper. J Clin Invest 2007;117:1746–1749.
23.
Rachmilewitz EA, Weizer-Stern O, Adamsky K, Amariglio N, Rechavi G, Breda L, Rivella S, Cabantchik ZI: 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;1054:118–123.
24.
dos Santos CO, Zhou S, Secolin R, Wang X, Cunha AF, Higgs DR, Kwiatkowski JL, Thein SL, Gallagher PG, Costa FF, Weiss MJ: Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function. Am J Hematol 2008;83:103–108.
25.
Rahav G, Volach V, Shapiro M, Rund D, Rachmilewitz EA, Goldfarb A: Severe infections in thalassaemic patients: prevalence and predisposing factors. Br J Haematol 2006;133:667–674.
26.
Farmakis D, Giakoumis A, Polymeropoulos E, Aessopos A: Pathogenetic aspects of immune deficiency associated with beta-thalassemia. Med Sci Monit 2003;9:RA19–RA22.
27.
Alidoost F, Gharagozloo M, Bagherpour B, Jafarian A, Sajjadi SE, Hourfar H, Moayedi B: Effects of silymarin on the proliferation and glutathione levels of peripheral blood mononuclear cells from beta-thalassemia major patients. Int Immunopharmacol 2006;6:1305–1310.
28.
Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brot N, Fitzgerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ 2nd, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC: Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med 2005;38:698–710.
29.
Kadiiska MB, Gladen BC, Baird DD, Graham LB, Parker CE, Ames BN, Basu S, Fitzgerald GA, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ 2nd, Rokach J, Shigenaga MK, Sun J, Walter PB, Tomer KB, Barrett JC, Mason RP: Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning. Free Radic Biol Med 2005;38:711–718.
30.
Traber MG, Atkinson J: Vitamin E, antioxidant and nothing more. Free Radic Biol Med 2007;43:4–15.
31.
Field CJ, Johnson IR, Schley PD: Nutrients and their role in host resistance to infection. J Leukoc Biol 2002;71:16–32.
32.
Fenech M, Dreosti I, Aitken C: Vitamin-E supplements and their effect on vitamin-E status in blood and genetic damage rate in peripheral blood lymphocytes. Carcinogenesis 1997;18:359–364.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.