Synergic Treatment of Plant-Based Antioxidants with Iron Chelators for Iron Overload in Transfusion-Dependent-Thalassemia Patients: A Systematic Review
-
Moe Thida Kyaw
,
Phyu Synn Oo
,
Carolina Santiago
,
Afshan Sumera
,
Anupa Sivakumar
,
Carolina Santiago
,
Yin Nwe Aung
Abstract
The combined use of plant-based antioxidants and iron chelators presents a synergistic treatment approach that effectively tackles both iron overload and the accompanying oxidative stress in individuals with transfusion-dependent Thalassemia (TDT). Plant-based antioxidants counteract reactive oxygen species (ROS) and oxidative damage, whereas iron chelators effectively bind excess iron, reducing the body's iron concentration. This combined therapy can be beneficial in improving TDT patients with iron overload. We systematically reviewed the literature exploring the plant-based antioxidants with iron chelators for iron overload in transfusion-dependent Thalassemia Patients. All fourteen included studies were randomized clinical trials, employing various randomization methods including simple randomization, double-blinded, triple-blinded, and crossover designs. The included studies enrolled participants across different age groups, including both young and adult patients. Despite the variability in plant-based antioxidants with iron-chelating properties, the key findings were as follows: Nine studies reported a significant reduction in iron overload, eight studies observed a marked decrease in oxidative stress markers, and five studies demonstrated reduced liver enzyme levels, suggesting potential hepatoprotective effects. All included studies reported significant effects of various supplements on key biomarkers, including total iron (Fe), ferritin, total iron-binding capacity (TIBC), total antioxidant capacity (TAC), malondialdehyde (MDA), and liver enzymes (AST, ALT). Silymarin, green tea, and grape seed extract (GSE) supplementation demonstrated notable reductions in total Fe, Ferritin, ASL, and ALT levels. Additionally, these supplements increased TIBC levels, suggesting improved iron metabolism. In contrast, quercetin and curcumin supplementation did not show a statistically significant difference compared to control groups in these outcomes.
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2. May N, de Sousa Alves Neri JL, Clunas H, et al. Investigating the Therapeutic Potential of Plants and Plant-Based Medicines: Relevance to Antioxidant and Neuroprotective Effects. Nutrients. 2023; 15(18):3912.
3. Srichairatanakool S, Ounjaijean S, Thephinlap C, et al. Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. Hemoglobin. 2006;30(2):311-327.
4. Saewong T, Ounjaijean S, Mundee Y, et al. Effects of green tea on iron accumulation and oxidative stress in livers of iron-challenged thalassemic mice. Med Chem. 2010;6(2):57-64.
5. Flora SJ, Pande M, Mehta A. Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication. Chem Biol Interact. 2003;145(3):267-80.
6. Gharagozloo M, Moayedi B, Zakerinia M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam Clin Pharmacol. 2009;23(3):359-65.
7. Hagag AA, Elfrargy MS, Gazar RA, et al. Therapeutic value of combined therapy with deferasirox and silymarin on iron overload in children with Beta thalassemia. Mediterr J Hematol Infect Dis. 2013;5(1):e2013065.
8. Hagag AA, Elfaragy MS, Elrifaey SM, et al. Therapeutic value of combined therapy with deferiprone and silymarin as iron chelators in Egyptian children with beta thalassemia major. Infect Disord Drug Targets. 2015;15(3):189-195.
9. Darvishi-Khezri H, Salehifar E, Kosaryan M, et al. Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomized control trial. Phytother Res. 2018;32(3):496-503.
10. Darvishi-Khezri H, Salehifar E, Kosaryan M, et al. The impact of silymarin on antioxidant and oxidative status in patients with β-thalassemia major: A crossover, randomized controlled trial. Complement Ther Med. 2017;35:25-32.
11. Moayedi B, Gharagozloo M, Esmaeil N, et al. A randomized double-blind, placebo-controlled study of therapeutic effects of silymarin in β-thalassemia major patients receiving desferrioxamine. Eur J Haematol. 2013;90(3):202-9.
12. Nasseri, E, Nasseri E, Mohammadi E, et al. Benefits of Curcumin Supplementation on Antioxidant Status in β-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial. Ann Nutr Metab. 2017;71(3-4):136-144.
13. Mohammadi E, Tamaddoni A, Qujeq D, et al. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytother Res. 2018;32(9):1828-1835.
14. Soeizi E, Maryam R, Jafarabadi MA, et al. Effects of Green Tea on Serum Iron Parameters and Antioxidant Status in Patients with β–Thalassemia Major. Pharmaceutical Sciences;2017. 23. 27-36.
15. Hezaveh ZS, Azarkeivan A, Janani L, et al. The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial. Complement Ther Med; 2019. 46:24-28.
16. Hezaveh ZS, Azarkeivan A, Janani L, et al. Effect of quercetin on oxidative stress and liver function in beta-thalassemia major patients receiving desferrioxamine: A double-blind randomized clinical trial. J Res Med Sci; 2019. Oct 25;24:91.
17. Sharifi-Zahabi E, Abdollahzad H, Mostafa Nachvak S, et al. Effects of alpha lipoic acid on iron overload, lipid profile and oxidative stress indices in β-thalassemia major patients: A cross-over randomised controlled clinical trial. Int J Clin Pract. 2021;75(6):e14062.
18. Satehi MB, Karimi M, Farrokhian Z, et al. The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial. Clin Nutr ESPEN. 2024; 61:230-236.
19. Mottaghi S, Abbaszadeh H. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Complement Ther Clin Pract. 2023; 53:101804.
20. 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(2):84-90.
21. Camini FC, Costa DC. Silymarin: not just another antioxidant. J Basic Clin Physiol Pharmacol. 2020;31(4):/j/jbcpp.2020.31.issue-4/jbcpp-2019-0206/jbcpp-2019-0206.xml.
22. Taleb A, Ahmad KA, Ihsan AU, et al. Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomed Pharmacother. 2018; 102: 689-698.
23. Shaker E, Mahmoud, H, Mnaa S. Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol. 2010; 48(3): 803–6.
24. Kim S, Oh DS, Oh J, et al. Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response. Molecules. 2016; 21(4): 443.
25. Wang, L, Huang QH, Li YX, et al. Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats. Mol Med Rep. 2018; 17(1):789-800.
26. Kwon D, Jung Y, Kim S, et al. Alterations in Sulfur Amino Acid Metabolism in Mice Treated with Silymarin: A Novel Mechanism of Its Action Involved in Enhancement of the Antioxidant Defense in Liver. Planta Med. 2013; 79(12): 997–1002.
27. Anand P, Thomas SG, Kunnumakkara A, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008; 76(11):1590–611.
28. Revathy S, Elumalai S, Benny M, et al. Evaluation of curcuminoids in turmeric rhizome (Curcuma longa L.) collected from different places in India. Biosci Biotech Res Asia. 2011; 8(1): 259–264.
29. Jin W, Wang J, Zhu T, et al. Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats. Inflamm Res. 2014;63(5):381-7.
30. Chan MMY, Adapala NS, Fong D. Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania. Parasitol Res. 2005; 96(1): 49–56.
31. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis. 2004; 6(4):367–77.
32. Jiao Y, Wilkinson J, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 2009; 113(2): 462–9.
33. Jiao Y, Wilkinson J, Di X, et al. Iron chelation in the biological activity of curcumin. Free Radic Biol Med. 2006; 40(7): 1152–60.
34. Jiao Y, Wilkinson J 4th, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 2009; 113(2):462–9.
35. Chin D, Huebbe P, Frank J, et al. Curcumin may impair iron status when fed to mice for six months. Redox Biol. 2014; 2: 563–9.
36. Weeraphan C, Srisomsap C, Chokchaichamnankit D, et al. Role of curcuminoids in ameliorating oxidative modification in β thalassemia /Hb E plasma proteome. J Nutr Biochem. 2013; 24(3): 578–85.
37. Hatairaktham S, Masaratana P, Hantaweepant C, et al. Curcuminoids supplementation ameliorates iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfusion-dependent β-thalassemia/Hb E patients. Ann Hematol. 2021; 100(4):891-901.
38. Bernatoniene J, Kopustinskiene D. The Role of Catechins in Cellular Responses to Oxidative Stress. Molecules. 2018; 23(4): 965.
39. Al-Momen H, Hussein HK, Al-Attar Z, et al. Green tea influence on iron overload in thalassemia intermedia patients: a randomized controlled trial. F1000Res. 2020 Sep 16; 9:1136.
40. Marouani N, Chahed A, Hédhili A, et a. Both aluminum and polyphenols in green tea decoction (Camellia sinensis) affect iron status and hematological parameters in rats. Eur J Nutr. 2007; 46(8): 453–9.
41. Koonyosying P, Kongkarnka S, Uthaipibull C, et al. Green tea extract modulates oxidative tissue injury in beta-thalassemic mice by chelation of redox iron and inhibition of lipid peroxidation. Biomed Pharmacother. 2018; 108: 1694–1702.
42. Ezzati Nazhad Dolatabadi J, Mokhtarzadeh A, Ghareghoran SM, et al. Synthesis, characterization and antioxidant property of quercetin-Tb(III) complex. Adv Pharm Bull. 2014;4(2):101–4.
43. Leopoldini M, Russo N, Chiodo S, et al. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem. 2006;54(17):6343–51.
44. Zhang Y, Li H, Zhao Y, et al. Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury. Eur J Pharmacol. 2006;535(1-3):263–9.
45. Lesjak M, Hoque R, Balesaria S, et al. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS One. 2014;9(7):e102900.
46. McIlduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy. Ther Clin Risk Manag. 2011;7:377-85.
47. Lal A, Atamna W, Killilea DW, et al. Lipoic acid and acetyl-carnitine reverse iron-induced oxidative stress in human fibroblasts. Redox Rep. 2008;13(1):2-10.
48. Ali YF, Desouky OS, Selim NS, et al. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload. J Radiat Res Appl Sci. 2015;8(1):26-35.
49. Shay KP, Moreau RF, Smith EJ, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790 (10):1149-60.
50. Wang T, Cheng J, Wang S, et al. α-Lipoic acid attenuates oxidative stress and neurotoxicity via the ERK/Akt-dependent pathway in the mutant hSOD1 related Drosophila model and the NSC34 cell line of amyotrophic lateral sclerosis. Brain Res Bull. 2018;140:299-310.
51. De Sanctis V, Kattamis C, Canatan D, et al. Bthalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017;9(1) :e2017018.
52. Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med. 2012;2(9):a011692.
53. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6.
54. Yin P, Wang Y, Yang L, et al. Hypoglycemic effects in Alloxan-Induced Diabetic Rats of the Phenolic Extract from mongolian oak cups enriched in ellagic acid, kaempferol and their derivatives. Molecules. 2018;23(5):1046.
55. Abolghasemi H, Amid A, Zeinali S, et al. Thalassemia in Iran: epidemiology, prevention, and management. J Pediatr Hematol Oncol. 2007;29(4):233-8.
56. Gupta KK, Mishra A, Tiwari A. Production of reactive oxygen species, its effect, drugs and plant extract used as an antioxidant, chelator on thalassemic patient: A review. Int J Pharmaceut Sci Res. 2011;2(9):2278-2285.
57. Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harbor Perspect Med. 2013;3(2):a011775
58. Razmaraii N, Babaei H, Nayebi AM, et al. Cardioprotective effect of grape seed extract on chronic doxorubicin-induced cardiac toxicity in Wistar rats. Adv Pharm Bull. 2016; 6 (3): 423-433.
59. Ma ZF, Zhang H. Phytochemical constituents, health benefits, and industrial applications of grape seeds: A mini-review. Antioxidants (Basel). 2017;6(3):71.
60. Chen J, Thilakarathna W, Astatkie T, et al. Optimization of catechin and proanthocyanidin recovery from grape seeds using microwave-assisted extraction. Biomolecules. 2020;10 (2):243.
61. Unusan N. Proanthocyanidins in grape seeds: an updated review of their health benefits and potential uses in the food industry. J Funct Foods. 2020;67:103861.
62. Wu TH, Liao JH, Hsu FL, et al. Grape seed proanthocyanidin extract chelates iron and attenuates the toxic effects of 6- hydroxydopamine: implications for Parkinson’s disease. J Food Biochem. 2010;34 (2) : 244–262.
63. Yun S, Chu D, He X, et al. Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats. J Trace Elem Med Biol. 2020; 57 : 126407.
64. Niu Q, He P, Xu S, et al. Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of grape seed proanthocyanidin extract. J Toxicol Sci. 2018; 43 (5): 311–319.
65. Pfukwa TM, Fawole OA, Manley M, et al. Food preservative capabilities of grape (Vitis vinifera) and clementine Mandarin (Citrus reticulata) by-products extracts in South Africa. Sustainability. 2019 ; 11 (6) : 1746
2. May N, de Sousa Alves Neri JL, Clunas H, et al. Investigating the Therapeutic Potential of Plants and Plant-Based Medicines: Relevance to Antioxidant and Neuroprotective Effects. Nutrients. 2023; 15(18):3912.
3. Srichairatanakool S, Ounjaijean S, Thephinlap C, et al. Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. Hemoglobin. 2006;30(2):311-327.
4. Saewong T, Ounjaijean S, Mundee Y, et al. Effects of green tea on iron accumulation and oxidative stress in livers of iron-challenged thalassemic mice. Med Chem. 2010;6(2):57-64.
5. Flora SJ, Pande M, Mehta A. Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication. Chem Biol Interact. 2003;145(3):267-80.
6. Gharagozloo M, Moayedi B, Zakerinia M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam Clin Pharmacol. 2009;23(3):359-65.
7. Hagag AA, Elfrargy MS, Gazar RA, et al. Therapeutic value of combined therapy with deferasirox and silymarin on iron overload in children with Beta thalassemia. Mediterr J Hematol Infect Dis. 2013;5(1):e2013065.
8. Hagag AA, Elfaragy MS, Elrifaey SM, et al. Therapeutic value of combined therapy with deferiprone and silymarin as iron chelators in Egyptian children with beta thalassemia major. Infect Disord Drug Targets. 2015;15(3):189-195.
9. Darvishi-Khezri H, Salehifar E, Kosaryan M, et al. Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomized control trial. Phytother Res. 2018;32(3):496-503.
10. Darvishi-Khezri H, Salehifar E, Kosaryan M, et al. The impact of silymarin on antioxidant and oxidative status in patients with β-thalassemia major: A crossover, randomized controlled trial. Complement Ther Med. 2017;35:25-32.
11. Moayedi B, Gharagozloo M, Esmaeil N, et al. A randomized double-blind, placebo-controlled study of therapeutic effects of silymarin in β-thalassemia major patients receiving desferrioxamine. Eur J Haematol. 2013;90(3):202-9.
12. Nasseri, E, Nasseri E, Mohammadi E, et al. Benefits of Curcumin Supplementation on Antioxidant Status in β-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial. Ann Nutr Metab. 2017;71(3-4):136-144.
13. Mohammadi E, Tamaddoni A, Qujeq D, et al. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytother Res. 2018;32(9):1828-1835.
14. Soeizi E, Maryam R, Jafarabadi MA, et al. Effects of Green Tea on Serum Iron Parameters and Antioxidant Status in Patients with β–Thalassemia Major. Pharmaceutical Sciences;2017. 23. 27-36.
15. Hezaveh ZS, Azarkeivan A, Janani L, et al. The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial. Complement Ther Med; 2019. 46:24-28.
16. Hezaveh ZS, Azarkeivan A, Janani L, et al. Effect of quercetin on oxidative stress and liver function in beta-thalassemia major patients receiving desferrioxamine: A double-blind randomized clinical trial. J Res Med Sci; 2019. Oct 25;24:91.
17. Sharifi-Zahabi E, Abdollahzad H, Mostafa Nachvak S, et al. Effects of alpha lipoic acid on iron overload, lipid profile and oxidative stress indices in β-thalassemia major patients: A cross-over randomised controlled clinical trial. Int J Clin Pract. 2021;75(6):e14062.
18. Satehi MB, Karimi M, Farrokhian Z, et al. The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial. Clin Nutr ESPEN. 2024; 61:230-236.
19. Mottaghi S, Abbaszadeh H. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Complement Ther Clin Pract. 2023; 53:101804.
20. 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(2):84-90.
21. Camini FC, Costa DC. Silymarin: not just another antioxidant. J Basic Clin Physiol Pharmacol. 2020;31(4):/j/jbcpp.2020.31.issue-4/jbcpp-2019-0206/jbcpp-2019-0206.xml.
22. Taleb A, Ahmad KA, Ihsan AU, et al. Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomed Pharmacother. 2018; 102: 689-698.
23. Shaker E, Mahmoud, H, Mnaa S. Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol. 2010; 48(3): 803–6.
24. Kim S, Oh DS, Oh J, et al. Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response. Molecules. 2016; 21(4): 443.
25. Wang, L, Huang QH, Li YX, et al. Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats. Mol Med Rep. 2018; 17(1):789-800.
26. Kwon D, Jung Y, Kim S, et al. Alterations in Sulfur Amino Acid Metabolism in Mice Treated with Silymarin: A Novel Mechanism of Its Action Involved in Enhancement of the Antioxidant Defense in Liver. Planta Med. 2013; 79(12): 997–1002.
27. Anand P, Thomas SG, Kunnumakkara A, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008; 76(11):1590–611.
28. Revathy S, Elumalai S, Benny M, et al. Evaluation of curcuminoids in turmeric rhizome (Curcuma longa L.) collected from different places in India. Biosci Biotech Res Asia. 2011; 8(1): 259–264.
29. Jin W, Wang J, Zhu T, et al. Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats. Inflamm Res. 2014;63(5):381-7.
30. Chan MMY, Adapala NS, Fong D. Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania. Parasitol Res. 2005; 96(1): 49–56.
31. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis. 2004; 6(4):367–77.
32. Jiao Y, Wilkinson J, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 2009; 113(2): 462–9.
33. Jiao Y, Wilkinson J, Di X, et al. Iron chelation in the biological activity of curcumin. Free Radic Biol Med. 2006; 40(7): 1152–60.
34. Jiao Y, Wilkinson J 4th, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 2009; 113(2):462–9.
35. Chin D, Huebbe P, Frank J, et al. Curcumin may impair iron status when fed to mice for six months. Redox Biol. 2014; 2: 563–9.
36. Weeraphan C, Srisomsap C, Chokchaichamnankit D, et al. Role of curcuminoids in ameliorating oxidative modification in β thalassemia /Hb E plasma proteome. J Nutr Biochem. 2013; 24(3): 578–85.
37. Hatairaktham S, Masaratana P, Hantaweepant C, et al. Curcuminoids supplementation ameliorates iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfusion-dependent β-thalassemia/Hb E patients. Ann Hematol. 2021; 100(4):891-901.
38. Bernatoniene J, Kopustinskiene D. The Role of Catechins in Cellular Responses to Oxidative Stress. Molecules. 2018; 23(4): 965.
39. Al-Momen H, Hussein HK, Al-Attar Z, et al. Green tea influence on iron overload in thalassemia intermedia patients: a randomized controlled trial. F1000Res. 2020 Sep 16; 9:1136.
40. Marouani N, Chahed A, Hédhili A, et a. Both aluminum and polyphenols in green tea decoction (Camellia sinensis) affect iron status and hematological parameters in rats. Eur J Nutr. 2007; 46(8): 453–9.
41. Koonyosying P, Kongkarnka S, Uthaipibull C, et al. Green tea extract modulates oxidative tissue injury in beta-thalassemic mice by chelation of redox iron and inhibition of lipid peroxidation. Biomed Pharmacother. 2018; 108: 1694–1702.
42. Ezzati Nazhad Dolatabadi J, Mokhtarzadeh A, Ghareghoran SM, et al. Synthesis, characterization and antioxidant property of quercetin-Tb(III) complex. Adv Pharm Bull. 2014;4(2):101–4.
43. Leopoldini M, Russo N, Chiodo S, et al. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem. 2006;54(17):6343–51.
44. Zhang Y, Li H, Zhao Y, et al. Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury. Eur J Pharmacol. 2006;535(1-3):263–9.
45. Lesjak M, Hoque R, Balesaria S, et al. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS One. 2014;9(7):e102900.
46. McIlduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy. Ther Clin Risk Manag. 2011;7:377-85.
47. Lal A, Atamna W, Killilea DW, et al. Lipoic acid and acetyl-carnitine reverse iron-induced oxidative stress in human fibroblasts. Redox Rep. 2008;13(1):2-10.
48. Ali YF, Desouky OS, Selim NS, et al. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload. J Radiat Res Appl Sci. 2015;8(1):26-35.
49. Shay KP, Moreau RF, Smith EJ, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790 (10):1149-60.
50. Wang T, Cheng J, Wang S, et al. α-Lipoic acid attenuates oxidative stress and neurotoxicity via the ERK/Akt-dependent pathway in the mutant hSOD1 related Drosophila model and the NSC34 cell line of amyotrophic lateral sclerosis. Brain Res Bull. 2018;140:299-310.
51. De Sanctis V, Kattamis C, Canatan D, et al. Bthalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017;9(1) :e2017018.
52. Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med. 2012;2(9):a011692.
53. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6.
54. Yin P, Wang Y, Yang L, et al. Hypoglycemic effects in Alloxan-Induced Diabetic Rats of the Phenolic Extract from mongolian oak cups enriched in ellagic acid, kaempferol and their derivatives. Molecules. 2018;23(5):1046.
55. Abolghasemi H, Amid A, Zeinali S, et al. Thalassemia in Iran: epidemiology, prevention, and management. J Pediatr Hematol Oncol. 2007;29(4):233-8.
56. Gupta KK, Mishra A, Tiwari A. Production of reactive oxygen species, its effect, drugs and plant extract used as an antioxidant, chelator on thalassemic patient: A review. Int J Pharmaceut Sci Res. 2011;2(9):2278-2285.
57. Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harbor Perspect Med. 2013;3(2):a011775
58. Razmaraii N, Babaei H, Nayebi AM, et al. Cardioprotective effect of grape seed extract on chronic doxorubicin-induced cardiac toxicity in Wistar rats. Adv Pharm Bull. 2016; 6 (3): 423-433.
59. Ma ZF, Zhang H. Phytochemical constituents, health benefits, and industrial applications of grape seeds: A mini-review. Antioxidants (Basel). 2017;6(3):71.
60. Chen J, Thilakarathna W, Astatkie T, et al. Optimization of catechin and proanthocyanidin recovery from grape seeds using microwave-assisted extraction. Biomolecules. 2020;10 (2):243.
61. Unusan N. Proanthocyanidins in grape seeds: an updated review of their health benefits and potential uses in the food industry. J Funct Foods. 2020;67:103861.
62. Wu TH, Liao JH, Hsu FL, et al. Grape seed proanthocyanidin extract chelates iron and attenuates the toxic effects of 6- hydroxydopamine: implications for Parkinson’s disease. J Food Biochem. 2010;34 (2) : 244–262.
63. Yun S, Chu D, He X, et al. Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats. J Trace Elem Med Biol. 2020; 57 : 126407.
64. Niu Q, He P, Xu S, et al. Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of grape seed proanthocyanidin extract. J Toxicol Sci. 2018; 43 (5): 311–319.
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| Files | ||
| Issue | Vol 19 No 3 (2025) | |
| Section | Review Article(s) | |
| Keywords | ||
| Plant-based antioxidant; Transfusion-dependent thalassemia; Supplement | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Kyaw M, Oo P, Santiago C, Sumera A, Sivakumar A, Santiago C, Aung Y. Synergic Treatment of Plant-Based Antioxidants with Iron Chelators for Iron Overload in Transfusion-Dependent-Thalassemia Patients: A Systematic Review. Int J Hematol Oncol Stem Cell Res. 2025;19(3):261-285.
