**Author details**

Somdet Srichairatanakool1 and Suthat Fucharoen2\*

\*Address all correspondence to: suthat.fuc@mahidol.ac.th

1 Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

2 Thalassemia Research Center, Institute of Molecular Bioscience, Mahidol University, Na‐ kornpathom, Thailand

### **References**

[1] Aisen P, Enns C, Wessling-Resnick M. Chemistry and Biology of Eukaryotic Iron Me‐ tabolism. International Journal of Biochemistry and Cell Biology 2001;33(10) 940-959

Macrophages by Erythropoietin in Rats. Journal of Cell Biochemistry 2008;104(2)

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

145

[16] Beutler E. Iron Storage Disease: Facts, Fiction and Progress. Blood Cells, Molecules &

[17] Hershko C, Konijn AM, Link G. Iron Chelators for Thalassaemia. British Journal of

[18] Hershko C, Graham G, Bates GW, Rachmilewitz EA. Non-Specific Serum Iron in Thalassaemia: an Abnormal Serum Iron Fraction of Potential Toxicity. British Journal

[19] Breuer W, Hershko C, Cabantchik ZI. The Importance of Non-Transferrin Bound Iron in Disorders of Iron Metabolism. Transfusion Science 2000;23(3) 185-192

[20] Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI. La‐ bile Plasma Iron in Iron Overload: Redox Activity and Susceptibility to Chelation.

[21] Kushner JP, Porter JP, Olivieri NF. Secondary Iron Overload. Hematology American

[22] Weatherall DJ. Pathophysiology of Thalassaemia. Bailliere's Clinical Haematology

[23] Kalinowski DS, Richardson DR. The Evolution of Iron Chelators for The Treatment of Iron Overload Disease and Cancer. Pharmacology Review 2005;57(4) 547-583

[24] Papanikolaou G, Pantopoulos K. Iron Metabolism and Toxicity. Toxicology and Ap‐

[25] Schellhammer PF, Engle MA, Hagstrom JW. Histochemical Studies of the Myocardi‐ um and Conduction System in Acquired Iron-Storage Disease. Circulation 1967;35(4)

[26] Kremastinos DT, Toutouzas PK, Vyssoulis GP, Venetis CA, Avgoustakis DG. Iron Overload and Left Ventricular Performance in beta Thalassemia. Acta Cardiology

[27] Sonakul D, Pacharee P, Thakerngpol K. Pathologic Findings in 76 Autopsy Cases of

[28] Bannerman RM, Keusch G, Kreimer-Birnbaum M, Vance VK, Vaughan S. Thalasse‐ mia Intermedia, with Iron Overload, Cardiac Failure, Diabetes Mellitus, Hypopitui‐

[29] Aldouri MA, Wonke B, Hoffbrand AV, Flynn DM, Ward SE, Agnew JE, et al. High Incidence of Cardiomyopathy in beta-Thalassaemia Patients Receiving Regular

tarism and Porphyrinuria. American Journal of Medicine 1967;42(3) 476-486

Thalassemia. Birth Defects: Original Article Series 1988;23(5B) 157-176

Society of Hematology Education Program 2001 47-61

plied Pharmacology 2005;202(2) 199-211

629-641

Diseases 2007;39(2) 140-147

Haematology 1998;101(3) 399-406

of Haematology 1978;40(2) 255-263

Blood 2003;102(7) 2670-2677

1998;11(1) 127-146

631-637

1984;39(1) 29-40


Macrophages by Erythropoietin in Rats. Journal of Cell Biochemistry 2008;104(2) 629-641

[16] Beutler E. Iron Storage Disease: Facts, Fiction and Progress. Blood Cells, Molecules & Diseases 2007;39(2) 140-147

**References**

297-308

ogy 2007;82(12 Suppl) 1147-1148

144 Pharmacology and Nutritional Intervention in the Treatment of Disease

1999;341(26) 1986-1995

1997;17(6) 407-421

1979;62(2) 100-105

2009;80(4) 339-344

lassemia Major. Blood 1976;47(3) 495-505

299-306

jury. Biomedical Pharmacotherapy 2001;55(6) 333-339

[1] Aisen P, Enns C, Wessling-Resnick M. Chemistry and Biology of Eukaryotic Iron Me‐ tabolism. International Journal of Biochemistry and Cell Biology 2001;33(10) 940-959

[2] Beutler E. History of Iron in Medicine. Blood Cells, Molecules & Diseases 2002;29(3)

[3] Hershko C. Iron Loading and Its Clinical Implications. American Journal of Hematol‐

[4] Emerit J, Beaumont C, Trivin F. Iron Metabolism, Free Radicals, and Oxidative In‐

[5] Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P. LPI-Labile Plasma Iron in Iron Overload. Best Practice & Research. Clinical Haematology 2005;18(2) 277-287

[6] Andrews NC. Disorders of Iron Metabolism. New England Journal of Medicine

[7] Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body Iron Metabolism and Patho‐ physiology of Iron Overload. International Journal of Hematology 2008;88(1) 7-15 [8] Porter JB. A Risk-Benefit Assessment of Iron-Chelation Therapy. Drug Safety

[9] Cranfield LM, Gollan JL, White AG, Dormandy TL. Serum Antioxidant Activity in Normal and Abnormal Subjects. Annual Review of Clinical Biochemistry 1979;16(6)

[10] Gerli GC, Beretta L, Bianchi M, Pellegatta A, Agostoni A. Erythrocyte Superoxide Dismutase, Catalase and Glutathione Peroxidase Activities in beta-Thalassaemia

[11] Katerelos C, Constantopoulos A, Agathopoulos A, Constantzas N, Zannos-Mariolea L, Matsaniotis N. Serum Levels of Retinol, Retinol-Binding Protein, Carotenoids and Triglycerides in Children with beta-Thalassemia Major. Acta Haematologica

[12] Rachmilewitz EA, Shohet SB, Lubin BH. Lipid Membrane Peroxidation in beta-Tha‐

[13] Weatherall DJ, Pressley L, Wood WG, Higgs DR, Clegg JB. Molecular Basis for Mild

[14] Muncie HL, Jr., Campbell J. Alpha and beta Thalassemia. American Family Physician

[15] Kong WN, Zhao SE, Duan XL, Yang Z, Qian ZM, Chang YZ. Decreased DMT1 and Increased Ferroportin 1 Expression Is the Mechanisms of Reduced Iron Retention in

Forms of Homozygous beta-Thalassaemia. Lancet 1981;1(8219) 527-529

(Major and Minor). Scandinavian Journal of Haematology 1980;25(1) 87-92


Transfusion and Iron Chelation: Reversal by Intensified Chelation. Acta Haematolog‐ ica 1990;84(3) 113-117

[43] Hebbel RP. Auto-Oxidation and a Membrane-Associated 'Fenton Reagent': a Possible Explanation for Development of Membrane Lesions in Sickle Erythrocytes. Clinical

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

147

[44] Hershko CM, Link GM, Konijn AM, Cabantchik ZI. Iron Chelation Therapy. Current

[45] Henrotin Y, Deberg M, Mathy-Hartert M, Deby-Dupont G. Biochemical Biomarkers of Oxidative Collagen Damage. Advances in Clinical Chemistry 2009;49 31-55

[46] Zhang AS, Sheftel AD, Ponka P. Intracellular Kinetics of Iron in Reticulocytes: Evi‐ dence for Endosome Involvement in Iron Targeting to Mitochondria. Blood

[47] Napier I, Ponka P, Richardson DR. Iron Trafficking in the Mitochondrion: Novel

[48] Cappellini MD, Tavazzi D, Duca L, Graziadei G, Mannu F, Turrini F, et al. Metabolic Indicators of Oxidative Stress Correlate with Haemichrome Attachment to Mem‐ brane, Band 3 Aggregation and Erythrophagocytosis in beta-Thalassaemia Interme‐

[49] Carpino A, Tarantino P, Rago V, De Sanctis V, Siciliano L. Antioxidant Capacity in Seminal Plasma of Transfusion-Dependent beta-Thalassemic Patients. Experimental

[50] Chakraborty I, Mitra S, Gachhui R, Kar M. Non-Haem Iron-Mediated Oxidative Stress in Haemoglobin E beta-Thalassaemia. Annals of the Academy of Medicine,

[51] Cheng ML, Ho HY, Tseng HC, Lee CH, Shih LY, Chiu DT. Antioxidant Deficit and Enhanced Susceptibility to Oxidative Damage in Individuals with Different Forms of

[52] Chiou SS, Chang TT, Tsai SP, Jang RC, Lin SK, Lee SC, et al. Lipid Peroxidation and Antioxidative Status in beta-Thalassemia Major Patients with or without Hepatitis C Virus Infection. Clinical Chemistry and Laboratory Medicine 2006;44(10) 1226-1233

[53] Altamentova SM, Shaklai N. Oxidative Stress in beta-Thalassemia: Hemoglobin al‐ pha-Chains Activate Peroxidation of Low Density Lipoproteins. Biofactors

[54] Abdalla MY, Fawzi M, Al-Maloul SR, El-Banna N, Tayyem RF, Ahmad IM. Increased Oxidative Stress and Iron Overload in Jordanian beta-Thalassemic Children. Hemo‐

[55] Bazrgar M, Karimi M, Peiravian F, Fathzadeh M. Apolipoprotein E Gene Polymor‐ phism and Left Ventricular Function in Iranian Patients with Thalassemia Major.

alpha-Thalassaemia. British Journal of Haematology 2005;128(1) 119-127

Haematology 1985;14(1) 129-140

2005;105(1) 368-375

Singapore 2010;39(1) 13-16

1998;8(1-2) 169-172

globin 2011;35(1) 67-79

Haematologica 2007;92(2) 256-257

Hematologic Malignancy Reports 2005;4(2) 110-116

Pathways Revealed by Disease. Blood 2005;105(5) 1867-1874

dia. British Journal of Haematology 1999;104(3) 504-512

and Clinical Endocrinology and Diabetes 2004;112(3) 131-134


[43] Hebbel RP. Auto-Oxidation and a Membrane-Associated 'Fenton Reagent': a Possible Explanation for Development of Membrane Lesions in Sickle Erythrocytes. Clinical Haematology 1985;14(1) 129-140

Transfusion and Iron Chelation: Reversal by Intensified Chelation. Acta Haematolog‐

[30] Kremastinos DT, Tiniakos G, Theodorakis GN, Katritsis DG, Toutouzas PK. Myocar‐ ditis in beta-Thalassemia Major. A Cause of Heart Failure. Circulation 1995;91(1)

[31] Rines AK, Ardehali H. Transition Metals and Mitochondrial Metabolism in the

[32] Bartfay WJ, Bartfay E. Iron-Overload Cardiomyopathy: Evidence for a Free Radical-Mediated Mechanism of Injury and Dysfunction in a Murine Model. Biological Re‐

[33] Nienhuis AW, Griffith P, Strawczynski H, Henry W, Borer J, Leon M, et al. Evalua‐ tion of Cardiac Function in Patients with Thalassemia Major. Annals of the New

[34] Senior R, Batabyal SK, Dutta RN, Guha S, Dutta S, Bhattacharji TD, et al. An Echo-Cardiographic (M-mode & 2D) Analysis of Thalassaemia Major. Indian Heart Journal

[35] Wielopolski L, Zaino EC. Noninvasive in-Vivo Measurement of Hepatic and Cardiac

[36] Lattanzi F, Bellotti P, Picano E, Chiarella F, Mazzarisi A, Melevendi C, et al. Quanti‐ tative Ultrasonic Analysis of Myocardium in Patients with Thalassemia Major and

[37] Lombardo T, Tamburino C, Bartoloni G, Morrone ML, Frontini V, Italia F, et al. Car‐ diac Iron Overload in Thalassemic Patients: an Endomyocardial Biopsy Study. An‐

[38] Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, et al. Cardio‐ vascular T2-Star (T2\*) Magnetic Resonance for the Early Diagnosis of Myocardial

[39] Wolfe L, Olivieri N, Sallan D, Colan S, Rose V, Propper R, et al. Prevention of Car‐ diac Disease by Subcutaneous Deferoxamine in Patients with Thalassemia Major.

[40] Freeman AP, Giles RW, Berdoukas VA, Talley PA, Murray IP. Sustained Normaliza‐ tion of Cardiac Function by Chelation Therapy in Thalassaemia Major. Clinical and

[41] Halliwell B, Gutteridge JM. Biologically Relevant Metal Ion-Dependent Hydroxyl

[42] Rund D, Rachmilewitz E. Pathophysiology of alpha- and beta-Thalassemia: Thera‐

Heart. Journal of Molecular and Cellular Cardiology 2012;(55) 50-57

ica 1990;84(3) 113-117

1990;42(1) 73-76

search for Nursing 2000;2(1) 49-59

146 Pharmacology and Nutritional Intervention in the Treatment of Disease

York Academy of Sciences 1980;344 384-396

Iron Overload. Circulation 1993;87(3) 748-754

nals of Hematology 1995;71(3) 135-141

Iron. Journal of Nuclear Medicine 1992;33(7) 1278-1282

Iron Overload. European Heart Journal 2001; 22(23) 2171-2179

Radical Generation. An update. FEBS Letters 1992;307(1) 108-112

peutic Implications. Seminar in Hematology 2001;38(4) 343-349

New England Journal of Medicine 1985;312(25) 1600-1603

Laboratory Haematology 1989;11(4) 299-307

66-71


[56] Haghpanah S, Davani M, Samadi B, Ashrafi A, Karimi M. Serum Lipid Profiles in Pa‐ tients with beta-Thalassemia Major and Intermedia in Southern Iran. Journal of Re‐ search in Medical Sciences 2011;15(3) 150-154

Cytoprotective Response in beta-Thalassemic Erythropoiesis. Haematologica

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

149

[69] Galanello R, Campus S. Deferiprone Chelation Therapy for Thalassemia Major. Acta

[70] Cappellini MD, Taher A. Deferasirox (Exjade) for the Treatment of Iron Overload.

[71] Viprakasit V, Lee-Lee C, Chong QT, Lin KH, Khuhapinant A. Iron Chelation Therapy in the Management of Thalassemia: the Asian Perspectives. International Journal of

[72] Hershko C, Abrahamov A, Konijn AM, Breuer W, Cabantchik IZ, Pootrakul P, et al. Objectives and Methods of Iron Chelation Therapy. Bioinorganic Chemistry and Ap‐

[73] Hershko C, Rachmilewitz EA. Iron Chelation in Thalassemia: Mechanism of Desfer‐ rioxamine Action. Israel Journal of Medical Science 1978;14(11) 1111-1115

[74] Summers MR, Jacobs A, Tudway D, Perera P, Ricketts C. Studies in Desferrioxamine and Ferrioxamine Metabolism in Normal and Iron-Loaded Subjects. British Journal

[75] Porter JB, Jaswon MS, Huehns ER, East CA, Hazell JW. Desferrioxamine Ototoxicity: Evaluation of Risk Factors in Thalassaemic Patients and Guidelines for Safe Dosage.

[76] Freedman MH, Grisaru D, Olivieri N, MacLusky I, Thorner PS. Pulmonary Syn‐ drome in Patients with Thalassemia Major Receiving Intravenous Deferoxamine In‐

[77] Olivieri NF, Buncic JR, Chew E, Gallant T, Harrison RV, Keenan N, et al. Visual and Auditory Neurotoxicity in Patients Receiving Subcutaneous Deferoxamine Infusions.

[78] Olivieri NF, Berriman AM, Tyler BJ, Davis SA, Francombe WH, Liu PP. Reduction in Tissue Iron Stores with a New Regimen of Continuous Ambulatory Intravenous De‐

[79] Hoffbrand AV, Cohen A, Hershko C. Role of Deferiprone in Chelation Therapy for

[80] Kolnagou A, Fessas C, Papatryphonas A, Economides C, Kontoghiorghes GJ. Pro‐ phylactic Use of Deferiprone (L1) and Magnetic Resonance Imaging T2\* or T2 for Preventing Heart Disease in Thalassaemia. British Journal of Haematology

fusions. American Journal of Diseases of Children 1990;144(5) 565-569

2011;96(11) 1595-1604

Haematologica 2009;122(2-3) 155-164

Hematology 2009;90(4) 435-445

of Haematology 1979;42(4) 547-555

British Journal of Haematology 1989;73(3) 403-409

New England Journal of Medicine 1986;314(14) 869-873

Transfusional Iron Overload. Blood 2003;102(1) 17-24

feroxamine. American Journal of Hematology 1992;41(1) 61-63

plications 2003:151-168

2004;127(3) 360-361

Acta Haematologica 2009;122(2-3) 165-173


Cytoprotective Response in beta-Thalassemic Erythropoiesis. Haematologica 2011;96(11) 1595-1604

[69] Galanello R, Campus S. Deferiprone Chelation Therapy for Thalassemia Major. Acta Haematologica 2009;122(2-3) 155-164

[56] Haghpanah S, Davani M, Samadi B, Ashrafi A, Karimi M. Serum Lipid Profiles in Pa‐ tients with beta-Thalassemia Major and Intermedia in Southern Iran. Journal of Re‐

[57] Afanas'ev IB. Superoxide and Nitric Oxide in Pathological Conditions Associated with Iron Overload: the Effects of Antioxidants and Chelators. Current Medicinal

[58] Afanas'ev IB. Interplay Between Superoxide and Nitric Oxide in Thalassemia and

[59] Afanas'ev IB, Afanas'ev, II, Deeva IB, Korkina LG. Free Radical Formation and Oxy‐ hemoglobin Oxidation in beta-Thalassemic Red Blood Cells in the Presence of Proox‐ idants: Effects of the Free Radical Scavenger Rutin and Oral Chelator L1. Transfusion

[60] Laksmitawati DR, Handayani S, Udyaningsih-Freisleben SK, Kurniati V, Adhiyanto C, Hidayat J, et al. Iron Status and Oxidative Stress in beta-Thalassemia Patients in

[61] Amer J, Goldfarb A, Fibach E. Flow Cytometric Analysis of the Oxidative Status of

[62] Amer J, Fibach E. Oxidative Status of Platelets in Normal and Thalassemic Blood.

[63] Amer J, Fibach E. Chronic Oxidative Stress Reduces the Respiratory Burst Response of Neutrophils from beta-Thalassaemia Patients. British Journal of Haematology

[64] Anderson D, Yardley-Jones A, Vives-Bauza C, Chua-Anusorn W, Cole C, Webb J. Ef‐ fect of Iron Salts, Haemosiderins, and Chelating Agents on the Lymphocytes of a Thalassaemia Patient without Chelation Therapy as Measured in the Comet Assay.

[65] Bartfay WJ, Lehotay DC, Sher GD, Bartfay E, Tyler B, Luo X, et al. Erythropoiesis: Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelat‐ ed with Deferoxamine or Deferiprone (L1) Versus NO Chelation. Hematology

[66] Claster S, Wood JC, Noetzli L, Carson SM, Hofstra TC, Khanna R, et al. Nutritional Deficiencies in Iron Overloaded Patients with Hemoglobinopathies. American Jour‐

[67] Awadallah SM, Nimer NA, Atoum MF, Saleh SA. Association of Haptoglobin Pheno‐ types with Ceruloplasmin Ferroxidase Activity in beta-Thalassemia Major. Clinica

[68] De Franceschi L, Bertoldi M, De Falco L, Santos Franco S, Ronzoni L, Turrini F, et al. Oxidative Stress Modulates Heme Synthesis and Induces Peroxiredoxin-2 as a Novel

Teratogenesis, Carcinogenesis, and Mutagenesis 2000;20(5) 251-264

Normal and Thalassemic Red Blood Cells. Cytometry A 2004;60(1) 73-80

search in Medical Sciences 2011;15(3) 150-154

Fanconi's Anemia. Hemoglobin 2006;30(1) 113-118

Thrombosis and Haemostasis 2004;92(5) 1052-1059

Chemistry 2005;12(23) 2731-2739

148 Pharmacology and Nutritional Intervention in the Treatment of Disease

Science 2000;23(3) 237-238

2005;129(3) 435-441

1999;4(1) 67-76

Jakarta. Biofactors 2003;19(1-2) 53-62

nal of Hematology 2009;84(6) 344-348

Chimica Acta 2011;412(11-12) 975-979


[81] Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F. Safety Profile of the Oral Iron Chelator Deferiprone: a Multicentre Study. British Journal of Haematology 2000;108(2) 305-312

[94] Brittenham GM, Sheth S, Allen CJ, Farrell DE. Noninvasive Methods for Quantitative Assessment of Transfusional Iron Overload in Sickle Cell Disease. Seminar in Hema‐

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

151

[95] Wood JC, Tyszka JM, Carson S, Nelson MD, Coates TD. Myocardial Iron Loading in Transfusion-dependent Thalassemia and Sickle Cell Disease. Blood 2004;103(5)

[96] Westwood M, Anderson LJ, Pennell DJ. Treatment of Cardiac Iron Overload in Tha‐

[97] Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring Long-Term Efficacy of Iron Che‐ lation Treatment with Biomagnetic Liver Susceptometry. Annals of the New York of

[98] Leonardi B, Margossian R, Colan SD, Powell AJ. Relationship of Magnetic Resonance Imaging Estimation of Myocardial Iron to Left Ventricular Systolic and Diastolic

[99] Schramm A, Matusik P, Osmenda G, Guzik TJ. Targeting NADPH Oxidases in Vas‐

[100] Dhaunsi GS, Kaur J, Alsaeid K, Turner RB, Bitar MS. Very Long Chain Fatty Acids Activate NADPH Oxidase in Human Dermal Fibroblasts. Cell Biochemistry and

[101] Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. gp91phox-Con‐ taining NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hyper‐

[102] Muzykantov VR. Targeting of Superoxide Dismutase and Catalase to Vascular Endo‐

[103] Cayatte AJ, Rupin A, Oliver-Krasinski J, Maitland K, Sansilvestri-Morel P, Boussard MF, et al. S17834, a New Inhibitor of Cell Adhesion and Atherosclerosis that Targets NADH Oxidase. Arteriosclerosis Thrombosis and Vascular Biology 2001;21(10)

[104] Zacharski LR, DePalma RG, Shamayeva G, Chow BK. The Statin-Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention. American Journal of Pub‐

[105] Wolf G. Free Radical Production and Angiotensin. Current Hypertension Report

[106] Brosnan MJ, Hamilton CA, Graham D, Lygate CA, Jardine E, Dominiczak AF. Irbe‐ sartan Lowers Superoxide Levels and Increases Nitric Oxide Bioavailability in Blood Vessels from Spontaneously Hypertensive Stroke-Prone Rats. Journal of Hyperten‐

Function in Thalassemia. JACC Cardiovascular Imaging 2008;1(5) 572-578

cular Pharmacology. Vascular Pharmacology 2013;56(5-6) 216-231

tology 2001;38(1 Supplement 1) 37-56

Academy of Sciences 2005;1054 350-357

tension. Circulation 2004;109(14) 1795-1801

thelium. Journal of Controlled Release 2001;71(1) 1-21

Function 2005;23(1) 65-68

lic Health 2013;103(4) e105-112

1577-1584

2000;2(2) 167-173

sion 2002;20(2) 281-286

lassemia Major. Haematologica 2003;88(5) 481-482

1934-1936


[94] Brittenham GM, Sheth S, Allen CJ, Farrell DE. Noninvasive Methods for Quantitative Assessment of Transfusional Iron Overload in Sickle Cell Disease. Seminar in Hema‐ tology 2001;38(1 Supplement 1) 37-56

[81] Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F. Safety Profile of the Oral Iron Chelator Deferiprone: a Multicentre Study. British Journal of Haematology

[82] Hoffbrand AV. Iron Chelation Therapy. Current Opinion in Hematology 1995;2(2)

[83] Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R, et al. Effectiveness and Safety of ICL670 in Iron-Loaded Patients with Thalassaemia: a Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Trial. Lancet

[84] Galanello R, Piga A, Alberti D, Rouan MC, Bigler H, Sechaud R. Safety, Tolerability, and Pharmacokinetics of ICL670, a New Orally Active Iron-Chelating Agent in Pa‐ tients with Transfusion-Dependent Iron Overload Due to beta-Thalassemia. Journal

[85] Barton JC. Deferasirox Novartis. Current Opinion in Investigational Drugs 2005;6(3)

[86] Galanello R. Evaluation of ICL670, a Once-Daily Oral Iron Chelator in a Phase III Clinical Trial of beta-Thalassemia Patients with Transfusional Iron Overload. Annals

[87] Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A Phase 3 Study of Deferasirox (ICL670), a Once-Daily Oral Iron Chelator, in Patients with be‐

[88] Porter JB. Deferasirox: An Effective Once-Daily Orally Active Iron Chelator. Drugs

[89] Wong C, Richardson DR. Beta-Thalassaemia: Emergence of New and Improved Iron Chelators for Treatment. International Journal of Biochemistry and Cell Biology

[90] Olivieri NF, Brittenham GM. Iron-Chelating Therapy and the Treatment of Thalasse‐

[91] Balocco M, Carrara P, Pinto V, Forni GL. Daily Alternating Deferasirox and Deferi‐ prone Therapy for "Hard-to-Chelate" beta-Thalassemia Major Patients. American

[92] Cappellini MD, Bejaoui M, Agaoglu L, Porter J, Coates T, Jeng M, et al. Prospective Evaluation of Patient-Reported Outcomes during Treatment with Deferasirox or De‐ feroxamine for Iron Overload in Patients with beta-Thalassemia. Clinical Therapeu‐

[93] Merson L, Olivier N. Orally Active Iron Chelators. Blood Review 2002;16(2) 127-134

2000;108(2) 305-312

150 Pharmacology and Nutritional Intervention in the Treatment of Disease

2003;361(9369) 1597-1602

of Clinical Pharmacology 2003;43(6) 565-572

ta-Thalassemia. Blood 2006;107(9) 3455-3462

Today (Barcelona, Spain: 1998) 2006;42(10) 623-637

of the New York Academy of Sciences 2005;1054 183-185

153-158

327-335

2003;35(7) 1144-1149

tics 2007;29(5) 909-917

mia. Blood 1997;89(3) 739-761

Journal of Hematology 2010;85(6) 460-461


[107] Oelze M, Daiber A, Brandes RP, Hortmann M, Wenzel P, Hink U, et al. Nebivolol In‐ hibits Superoxide Formation by NADPH Oxidase and Endothelial Dysfunction in Angiotensin II-Treated Rats. Hypertension 2006;48(4) 677-684

Chelation Therapy in the Comet Assay. Teratogenesis Carcinogenesis and Mutagene‐

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

153

[120] Bianco L, Boccaccini R, Capalbo P, Morici G, Maestro M, Mandrino M. [The Role of Vitamin E in the Therapy of Thalassemia]. Pediatria Medica e Chirurgica 1986;8(1)

[121] Cakmak A, Soker M, Koc A, Erel O. Paraoxonase and Arylesterase Activity with Oxi‐ dative Status in Children with Thalassemia Major. Journal of Pediatric Hematology/

[122] Cakmak A, Soker M, Koc A, Aksoy N. Prolidase Activity and Oxidative Status in Pa‐ tients with Thalassemia Major. Journal of Clinical Laboratory Analysis 2010;24(1)

[123] Das N, Das Chowdhury T, Chattopadhyay A, Datta AG. Attenuation of Oxidative Stress-Induced Changes in Thalassemic Erythrocytes by Vitamin E. Polish Journal of

[124] Kattamis C, Lazaropoulou C, Delaporta P, Apostolakou F, Kattamis A, Papassotiriou I. Disturbances of Biomarkers of Iron and Oxidant-Antioxidant Homeostasis in Pa‐ tients with beta-Thalassemia Intermedia. Pediatric Endocrinology Reviews 2011;8

[125] Kontoghiorghes GJ. Prospects for Introducing Deferiprone as Potent Pharmaceutical

[126] Suthutvoravut U, Hathirat P, Sirichakwal P, Sasanakul W, Tassaneeyakul A, Feung‐ pean B. Vitamin E Status, Glutathione Peroxidase Activity and the Effect of Vitamin E Supplementation in Children with Thalassemia. Journal of the Medical Association

[127] Vatanavicharn S, Yenchitsomanus P, Siddhikol C. Vitamin E in beta-Thalassaemia and alpha-Thalassaemia (HbH) Diseases. Acta Haematologica 1985;73(3) 183

[128] Phuapradit W, Panburana P, Jaovisidha A, Chanrachakul B, Bunyaratvej A, Puchai‐ watananon O. Serum Vitamin A and E in Pregnant Women with Hemoglobinopa‐

[129] Yenchitsomanus P, Wasi P. Increased Erythrocyte Superoxide Dismutase Activities in beta 0-Thalassaemia/Haemoglobin E and in Haemoglobin H Diseases. Journal of

[130] Dissayabutra T, Tosukhowong P, Seksan P. The Benefits of Vitamin C and Vitamin E in Children with beta-Thalassemia with High Oxidative Stress. Journal of the Medi‐

[131] Kalpravidh RW, Wichit A, Siritanaratkul N, Fucharoen S. Effect of Coenzyme Q10 as an Antioxidant in beta-Thalassemia/Hb E Patients. Biofactors 2005;25(1-4) 225-234

cal Association of Thailand 2005;88 Supplement 4 S317-321

thies. Journal of Obstetrics and Gynaecology Research 1999;25(3) 173-176

Antioxidant. Frontiers in Bioscience (Elite Edition) 2009;1 161-178

sis 2001;21(2) 165-174

Oncology 2009 31(8) 583-587

Pharmacology 2004;56(1) 85-96

of Thailand 1993;76 Supplement 2 146-152

Clinical Pathology 1983;36(3) 329-333

Supplemnt 2 256-262

23-26

6-11


Chelation Therapy in the Comet Assay. Teratogenesis Carcinogenesis and Mutagene‐ sis 2001;21(2) 165-174

[120] Bianco L, Boccaccini R, Capalbo P, Morici G, Maestro M, Mandrino M. [The Role of Vitamin E in the Therapy of Thalassemia]. Pediatria Medica e Chirurgica 1986;8(1) 23-26

[107] Oelze M, Daiber A, Brandes RP, Hortmann M, Wenzel P, Hink U, et al. Nebivolol In‐ hibits Superoxide Formation by NADPH Oxidase and Endothelial Dysfunction in

[108] Salvemini D, Muscoli C, Riley DP, Cuzzocrea S. Superoxide Dismutase Mimetics.

[109] Afifi AM, Ellis L, Huntsman RG, Said MI. High Dose Ascorbic Acid in the Manage‐ ment of Thalassaemia Leg Ulcers-a Pilot Study. British Journal of Dermatology

[110] Angelides NS, Angastiniotis C, Pavlides N. Effect of Pentoxifylline on Treatment of Lower Limb Ulcers in Patients with Thalassemia Major. Angiology 1992;43(7)

[111] Gerli GC, Mongiat R, Sandri MT, Agostoni A, Gualandri V, Orsini GB, et al. Antioxi‐ dant System and Serum Trace Elements in alpha-Thalassaemia and Hb Lepore Trait.

[112] Teng CM, Hsiao G, Ko FN, Lin DT, Lee SS. N-Allylsecoboldine as a Novel Antioxi‐ dant against Peroxidative Damage. European Journal of Pharmacology 1996;303(1-2)

[113] Tesoriere L, D'Arpa D, Maggio A, Giaccone V, Pedone E, Livrea MA. Oxidation Re‐ sistance of LDL is Correlated with Vitamin E Status in beta-Thalassemia Intermedia.

[114] Tesoriere L, D'Arpa D, Butera D, Allegra M, Renda D, Maggio A, et al. Oral Supple‐ ments of Vitamin E Improve Measures of Oxidative Stress in Plasma and Reduce Ox‐ idative Damage to LDL and Erythrocytes in beta-Thalassemia Intermedia Patients.

[115] Alidoost F, Gharagozloo M, Bagherpour B, Jafarian A, Sajjadi SE, Hourfar H, et al. Effects of Silymarin on the Proliferation and Glutathione Levels of Peripheral Blood Mononuclear Cells from beta-Thalassemia Major Patients. International Immuno‐

[116] Amer J, Atlas D, Fibach E. N-Acetylcysteine Amide (AD4) Attenuates Oxidative Stress in beta-Thalassemia Blood Cells. Biochimica Et Biophysica Acta 2008;1780(2)

[117] Amer J, Goldfarb A, Rachmilewitz EA, Fibach E. Fermented Papaya Preparation as Redox Regulator in Blood Cells of beta-Thalassemic Mice and Patients. Phytotherapy

[118] Amer J, Dana M, Fibach E. The Antioxidant Effect of Erythropoietin on Thalassemic

[119] Anderson D, Dhawan A, Yardley-Jones A, Ioannides C, Webb J. Effect of Antioxidant Flavonoids and a Food Mutagen on Lymphocytes of a Thalassemia Patient without

Angiotensin II-Treated Rats. Hypertension 2006;48(4) 677-684

Pulmonary Pharmacology & Therapeutics 2002;15(5) 439-447

European Journal of Haematology 1987;39(1) 23-27

Atherosclerosis 1998;137(2) 429-435

Free Radical Research 2001;34(5) 529-540

pharmacology 2006;6(8) 1305-1310

Research 2008;22(6) 820-828

Blood Cells. Anemia 2010;2010 978710

1975;92(3) 339-341

152 Pharmacology and Nutritional Intervention in the Treatment of Disease

549-554

129-139

249-255


[132] Ciavatta DJ, Ryan TM, Farmer SC, Townes TM. Mouse Model of Human beta Zero Thalassemia: Targeted Deletion of the Mouse beta Maj- and beta Min-Globin Genes in Embryonic Stem Cells. Proceedings of the National Academy of Sciences of the United States of America 1995;92(20) 9259-9263

tion in beta-Thalassemia/Hb E Plasma Proteome. Journal of Nutritional Biochemistry

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

155

[143] Unchern S, Laohareungpanya N, Sanvarinda Y, Pattanapanyasat K, Tanratana P, Chantharaksri U, et al. Oxidative Modification and Poor Protective Activity of HDL

[144] Srichairatanakool S, Ounjaijean S, Thephinlap C, Khansuwan U, Phisalpong C, Fu‐ charoen S. Iron-Chelating and Free-Radical Scavenging Activities of Microwave-

[145] Zuo Y, Chen H, Deng Y. Simultaneous Determination of Catechins, Caffeine and Gal‐ lic Acids in Green, Oolong, Black and Pu-erh Teas using HPLC with a Photodiode

[146] de Alarcon PA, Donovan ME, Forbes GB, Landaw SA, Stockman JA, 3rd. Iron Ab‐ sorption in the Thalassemia Syndromes and Its Inhibition by Tea. New England Jour‐

[147] Pippard MJ, Callender ST, Warner GT, Weatherall DJ. Iron Absorption and Loading

[148] Thephinlap C, Ounjaijean S, Khansuwan U, Fucharoen S, Porter JB, Srichairatanakool S. Epigallocatechin-3-gallate and Epicatechin-3-gallate from Green Tea Decrease Plas‐ ma NNon-Transferrin Bound Iron and Erythrocyte Oxidative Stress. Medicinal

[149] Ounjaijean S, Thephinlap C, Khansuwan U, Phisalapong C, Fucharoen S, Porter JB, et al. Effect of Green Tea on Iron Status and Oxidative Stress in Iron-Loaded Rats. Me‐

[150] Saewong T, Ounjaijean S, Mundee Y, Pattanapanyasat K, Fucharoen S, Porter JB, et al. Effects of Green Tea on Iron Accumulation and Oxidative Stress in Livers of Iron-

[151] Srichairatanakool S, Kulprachakarn K, Pangjit K, Pattanapanyasat K, Fuchaeron S. Green Tea Extract and Epigallocatechin 3-gallate Reduced Labile Iron Pool and Pro‐ tected Oxidative Stress in Iron-Loaded Cultured Hepatocytes. Advance in Bioscience

[152] Leiro JM, Alvarez E, Arranz JA, Siso IG, Orallo F. In Vitro Effects of Mangiferin on Superoxide Concentrations and Expression of the Inducible Nitric Oxide Synthase, Tumour Necrosis Factor-alpha and Transforming Growth Factor-beta Genes. Bio‐

[153] Leiro J, Arranz JA, Yanez M, Ubeira FM, Sanmartin ML, Orallo F. Expression Profiles of Genes Involved in the Mouse Nuclear Factor-kappa B Signal Transduction Path‐ way are Modulated by Mangiferin. International Immunopharmacology 2004;4(6)

Challenged Thalassemic Mice. Medicinal Chemistry 2010;6(2) 57-64

Processed Green Tea in Iron Overload. Hemoglobin 2006;30(2) 311-327

on LDL Oxidation in Thalassemia. Lipids 2010;45(7) 627-633

in beta-Thalassaemia Intermedia. Lancet 1979;2(8147) 819-821

Array Detector. Talanta 2002;57(4) 307-316

nal of Medicine 1979;300(1) 5-8

Chemistry 2007;3(3) 289-296

dicinal Chemistry 2008;4(4) 365-370

and Biotechnology 2012;3 1140-1150

763-778

chemical Pharmacology 2003;65(8) 1361-1371

2012;24(3) 578-585


tion in beta-Thalassemia/Hb E Plasma Proteome. Journal of Nutritional Biochemistry 2012;24(3) 578-585

[143] Unchern S, Laohareungpanya N, Sanvarinda Y, Pattanapanyasat K, Tanratana P, Chantharaksri U, et al. Oxidative Modification and Poor Protective Activity of HDL on LDL Oxidation in Thalassemia. Lipids 2010;45(7) 627-633

[132] Ciavatta DJ, Ryan TM, Farmer SC, Townes TM. Mouse Model of Human beta Zero Thalassemia: Targeted Deletion of the Mouse beta Maj- and beta Min-Globin Genes in Embryonic Stem Cells. Proceedings of the National Academy of Sciences of the

[133] Jamsai D, Zaibak F, Vadolas J, Voullaire L, Fowler KJ, Gazeas S, et al. A Humanized BAC Transgenic/Knockout Mouse Model for HbE/beta-Thalassemia. Genomics

[134] Jamsai D, Zaibak F, Khongnium W, Vadolas J, Voullaire L, Fowler KJ, et al. A Humanized Mouse Model for a Common beta0-Thalassemia Mutation. Genomics

[135] Vadolas J, Wardan H, Bosmans M, Zaibak F, Jamsai D, Voullaire L, et al. Transgene Copy Number-Dependent Rescue of Murine beta-Globin Knockout Mice Carrying a 183 kb Human beta-Globin BAC Genomic Fragment. Biochimica Et Biophysica Acta

[136] Wannasuphaphol B, Kalpravidh R, Pattanapanyasat K, Ioannau P, Kuypers FA, Fu‐ charoen S, et al. Rescued Mice with Hb E Transgene-Developed Red Cell Changes Similar to Human beta-Thalassemia/HbE Disease. Annals of the New York Academy

[137] Vogiatzi MG, Tsay J, Verdelis K, Rivella S, Grady RW, Doty S, et al. Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur during the Period of Bone Ac‐

[138] Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB, Srichairatanakool S. Efficacy of Curcuminoids in Alleviation of Iron Overload and Lipid Peroxidation in Thalasse‐

[139] Srichairatanakool S, Thephinlap C, Phisalaphong C, Porter JB, Fucharoen S. Curcu‐ min Contributes to In Vitro Removal of Non-Transferrin Bound Iron by Deferiprone and Desferrioxamine in Thalassemic Plasma. Medicinal Chemistry 2007;3(5) 469-474

[140] Thephinlap C, Phisalaphong C, Lailerd N, Chattipakorn N, Winichagoon P, Vadolus J, et al. Reversal of Cardiac Iron Loading and Dysfunction in Thalassemic Mice by

[141] Kalpravidh RW, Siritanaratkul N, Insain P, Charoensakdi R, Panichkul N, Hatairak‐ tham S, et al. Improvement in Oxidative Stress and Antioxidant Parameters in beta-Thalassemia/Hb E Patients Treated with Curcuminoids. Clinical Biochemistry

[142] Weeraphan C, Srisomsap C, Chokchaichamnankit D, Subhasitanont P, Hatairaktham S, Charoensakdi R, et al. Role of Curcuminoids in Ameliorating Oxidative Modifica‐

crual. Calcified Tissue International 2010;86(6) 484-494

mic Mice. Medicinal Chemistry 2009;5(5) 474-482

Curcuminoids. Medicinal Chemistry 2011;7(1) 62-69

United States of America 1995;92(20) 9259-9263

154 Pharmacology and Nutritional Intervention in the Treatment of Disease

2006;88(3) 309-315

2005;85(4) 453-461

2005;1728(3) 150-162

2009;43(4-5) 424-429

of Sciences 2005;1054 407-416


[154] Pardo-Andreu GL, Sanchez-Baldoquin C, Avila-Gonzalez R, Yamamoto ET, Revilla A, Uyemura SA, et al. Interaction of Vimang (Mangifera indica L. Extract) with Fe(III) Improves Its Antioxidant and Cytoprotecting Activity. Pharmacology Re‐ search 2006;54(5) 389-395

tients by Means of Electron Paramagnetic Resonance Spectroscopy. British Journal of

Antioxidants as Complementary Medication in Thalassemia

http://dx.doi.org/10.5772/57372

157

[167] Jirasomprasert T, Morales NP, Limenta LM, Sirijaroonwong S, Yamanont P, Wilairat P, et al. Pharmaco/Ferrokinetic-Related Pro-oxidant Activity of Deferiprone in beta-

[168] De Luca AC, Rusciano G, Ciancia R, Martinelli V, Pesce G, Rotoli B, et al. Spectro‐ scopical and Mechanical Characterization of Normal and Thalassemic Red Blood

[169] Selek S, Aslan M, Horoz M, Gur M, Erel O. Oxidative Status and Serum PON1 Activ‐ ity in beta-Thalassemia Minor. Clinical Biochemistry 2007;40(5-6) 287-291

[170] Labib HA, Etewa RL, Gaber OA, Atfy M, Mostafa TM, Barsoum I. Paraoxonase-1 and Oxidative Status in Common Mediterranean beta-Thalassaemia Mutations Trait, and Their Relations to Atherosclerosis. Journal of Clinical Pathology 2011;64(5) 437-442

[171] Prasartkaew S, Bunyaratvej A, Fucharoen S, Wasi P. Comparison of Erythrocyte An‐ tioxidative Enzyme Activities between Two Types of Haemoglobin H Disease. Jour‐

[172] Prasartkaew S, Bunyaratvej A, Fucharoen S, Wasi P. Oxidative Stress and Antioxida‐ tive Enzymes in Hemoglobin H Disease. Birth Defects: Original Article Series

[173] Ong-Ajyooth S, Suthipark K, Shumnumsirivath D, Likidlilid A, Fucharoen S, Pootra‐ kul P. Oxidative Stress and Antioxidants in beta-Thalassaemia/Haemoglobin E. Jour‐

[174] Sumboonnanonda A, Malasit P, Tanphaichitr VS, Ong-ajyooth S, Petrarat S, Vongjir‐ ad A. Renal Tubular Dysfunction in alpha-Thalassemia. Pediatric Nephrology

[175] Akrawinthawong K, Chaowalit N, Chatuparisuth T, Siritanaratkul N. Effectiveness of Deferiprone in Transfusion-Independent beta-Thalassemia/HbE Patients. Hema‐

[176] Kukongviriyapan V, Somparn N, Senggunprai L, Prawan A, Kukongviriyapan U, Jetsrisuparb A. Endothelial Dysfunction and Oxidant Status in Pediatric Patients with Hemoglobin E-beta Thalassemia. Pediatric Cardiology 2008;29(1) 130-135

[177] Phumala N, Porasuphatana S, Unchern S, Pootrakul P, Fucharoen S, Chantharaksri U. Hemin: a Possible Cause of Oxidative Stress in Blood Circulation of beta-Thalasse‐

[178] Luechapudiporn R, Morales NP, Fucharoen S, Chantharaksri U. The Reduction of Cholesteryl Linoleate in Lipoproteins: an Index of Clinical Severity in beta-Thalasse‐

mia/Hb E. Clinical Chemistry and Laboratory Medicine 2006;44(5) 574-581

mia/Hemoglobin E Disease. Free Radical Research 2003;37(2) 129-135

nal of the Medical Association of Thailand 1987;70(5) 270-274

Haematology 2005;131(1) 135-140

Thalassemia. Free Radical Research 2009;43(5) 485-491

nal of Clinical Pathology 1986;39(12) 1299-1303

1987;23(5A) 193-198

2003;18(3) 257-260

tology 2011;16(2) 113-122

Cells by Raman Tweezers. Optics Express 2008;16(11) 7943-7957


tients by Means of Electron Paramagnetic Resonance Spectroscopy. British Journal of Haematology 2005;131(1) 135-140

[167] Jirasomprasert T, Morales NP, Limenta LM, Sirijaroonwong S, Yamanont P, Wilairat P, et al. Pharmaco/Ferrokinetic-Related Pro-oxidant Activity of Deferiprone in beta-Thalassemia. Free Radical Research 2009;43(5) 485-491

[154] Pardo-Andreu GL, Sanchez-Baldoquin C, Avila-Gonzalez R, Yamamoto ET, Revilla A, Uyemura SA, et al. Interaction of Vimang (Mangifera indica L. Extract) with Fe(III) Improves Its Antioxidant and Cytoprotecting Activity. Pharmacology Re‐

[155] Pardo-Andreu GL, Delgado R, Nunez-Selles AJ, Vercesi AE. Mangifera indica L. Ex‐ tract (Vimang) Inhibits 2-Deoxyribose Damage Induced by Fe (III) Plus Ascorbate.

[156] Engels C, Knodler M, Zhao YY, Carle R, Ganzle MG, Schieber A. Antimicrobial Ac‐ tivity of Gallotannins Isolated from Mango ( Mangifera indica L.) Kernels. Journal of

[157] Schieber A, Berardini N, Carle R. Identification of Flavonol and Xanthone Glycosides from Mango (Mangifera indica L. Cv. "Tommy Atkins") Peels by High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry. Journal of Ag‐

[158] Jariwalla RJ. Rice-Bran Products: Phytonutrients with Potential Applications in Pre‐ ventive and Clinical Medicine. Drugs under Experimental and Clinical Research

[159] Wang HM, Lo WL, Huang LY, Wang YD, Chen CY. Chemical Constituents from the

[160] Borrelli R, Di Donato M, Peluso A. Role of Intramolecular Vibrations in Long-Range Electron Transfer between Pheophytin and Ubiquinone in Bacterial Photosynthetic

[161] Nelson RE, Ferruzzi MG. Synthesis and Bioaccessibility of Fe-Pheophytin Derivatives from Crude Spinach Extract. Journal of Food Science 2008;73(5) H86-H91

[162] Nozoye T, Inoue H, Takahashi M, Ishimaru Y, Nakanishi H, Mori S, et al. The Ex‐ pression of Iron Homeostasis-Related Genes during Rice Germination. Plant Molecu‐

[163] Marawaha RK, Bansal D, Kaur S, Trehan A. Wheat Grass Juice Reduces Transfusion Requirement in Patients with Thalassemia Major: a Pilot Study. Indian Journal of Pe‐

[164] Singh K, Pannu MS, Singh P, Singh J. Effect of Wheat Grass Tablets on the Frequency of Blood Transfusions in Thalassemia Major. Indian Journal of Pediatrics 2010;77(1)

[165] Choudhary DR, Naithani R, Panigrahi I, Kumar R, Mahapatra M, Pati HP, et al. Ef‐ fect of Wheat Grass Therapy on Transfusion Requirement in beta-Thalassemia Major.

[166] Filosa A, Valgimigli L, Pedulli GF, Sapone A, Maggio A, Renda D, et al. Quantitative Evaluation of Oxidative Stress Status on Peripheral Blood in beta-Thalassaemic Pa‐

Leaves of Michelia alba. Natural Product Research 2010;24(5) 398-406

search 2006;54(5) 389-395

2001;27(1) 17-26

lar Biology 2007;64(1-2) 35-47

diatrics 2004;41(7) 716-720

Indian Journal of Pediatrics 2009;76(4) 375-376

90-91

Phytotherapy Research 2006;20(2) 120-124

156 Pharmacology and Nutritional Intervention in the Treatment of Disease

Agricultural and Food Chemistry 2009;57(17) 7712-7718

ricultural and Food Chemistry 2003;51(17) 5006-5011

Reaction Centers. Biophysical Journal 2005;89(2) 830-841


[179] Morales NP, Charlermchoung C, Luechapudiporn R, Yamanont P, Fucharoen S, Chantharaksri U. Lipid Fluidity at Different Regions in LDL and HDL of beta-Tha‐ lassemia/Hb E Patients. Biochemical and Biophysical Research Communication 2006;350(3) 698-703

**Chapter 5**

**General Aspects of Ozone Therapy**

Additional information is available at the end of the chapter

concentration where rest of it is pure medical oxygen.

Ozone is a natural gas consisting of three oxygen atoms that has a distinctive odor. It is intrinsically hazardous over tolerable doses for living organisms. Ozone therapy is a medical therapy that a mixture of oxygen and ozone which is called medical ozone is used as a medical drug, more correctly pro-drug. Medical ozone contains less than 5% of ozone at maximum

The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived com‐ pounds able to act on several targets leading to a multifactorial correction of various patho‐ logical states. Ozone therapy can improve well-being and delay the negative effects of aging. Aging process basicly related with oxidants and anti-oxidants balance, Advanced Glycoslation End Substances (AGEs), role of genes and immune system, relevance of telomeres and

Ozone therapy is a general termination of a medical therapy that medical ozone gas is used as drug by several methods. Some of these methods are systemic where many others are local applications. Ozonated autohaemotherapy (O3-AHT) widely known by people firstly descri‐ bed by Wehrli and Steinbart and since 1954 it has been used in millions of patients in different pathologies with apparent clinical benefit. AHT might be applied in two forms, Major AHT simply driving 100-150 ml of venous blood into a sterile bottle made of neutral glass or other ozone resistant material where blood and medical ozone is mixed in therapeutic doses and then reinfused back to the donor without side effects. 3.13 % Natrium Citrate solution is used as an anticoagulant during the procedure with short lasting effect. In some patients Heparin

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

telomerase, hormones, nutrition, environmental factors and some other factors.

might be used instead of Natrium Citrate depending on the patient's case.

Ruhi Cakir

**1. Introduction**

http://dx.doi.org/10.5772/57470

**2. What is ozone therapy?**


**Chapter 5**
