Volume 4, Issue 2 (May 2019)                   JNFS 2019, 4(2): 142-151 | Back to browse issues page

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Sajadi Hezaveh Z, Shidfar F. Hydrophilic Phytochelators in Iron Overload Condition. JNFS. 2019; 4 (2) :142-151
URL: http://jnfs.ssu.ac.ir/article-1-255-en.html
Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
Abstract:   (35 Views)
Background: Iron overload can cause many complications and damage many organs as well as physiologic functions. Consumption of phetochemicals and flavonoids with iron chelating ability, instead of synthetic iron chelators, can be less harmful and more effective. The aim of this review is to investigate hydrophilic phytochelators in iron overload condition. Methods: In this review, the possible natural iron chelators including quercetin, rutin, bailcalin, silymarin, resveratrol, mimosine, tropolone, curcumine, catechin, kojic acid, and caffeic acid were investigated. Furthermore, the mechanisms through which they chelate iron were discussed. Results: The mentioned antioxidants eliminated excessive iron, decreased iron absorption, exerted antioxidant and anti-inflammatory activity without causing adverse effects and other metal deficiencies in iron overload condition. Conclusion: The combination of synthetic chelators with these antioxidants or their replacement with natural chelators could be possible treatments for iron overload
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Type of article: review article | Subject: public specific
Received: 2018/04/7 | Accepted: 2018/09/14 | Published: 2019/05/1

1. Adibi A, et al. 2012. Therapeutic effects of deferoxamine and silymarin versus deferoxamine alone in β-thalassemia major based on findings of liver MRI. Journal of research in medical sciences. 17 (1 SPL.1): S73-S78.
2. Afanas'ev IB, Afanas'ev II, Deeva IB & Korkina LG 2000. Free radical formation and oxyhemoglobin oxidation in β-thalassemic red blood cells in the presence of prooxidants: Effects of the free radical scavenger rutin and oral chelator L1. Transfusion science. 23 (3): 237-238.
3. Al-Basher GI 2019. Green tea activity and iron overload induced molecular fibrogenesis of rat liver. Saudi journal of biological sciences. 26 (3): 531-540.
4. Alta ECP, et al. 2014. Desferrioxamine-caffeine (DFCAF) as a cell permeant moderator of the oxidative stress caused by iron overload. BioMetals. 27 (6): 1351-1360.
5. Asai A & Miyazawa T 2000. Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life sciences. 67 (23): 2785-2793.
6. Barros-Rodríguez M, et al. 2014. Leucaena leucocephala in ruminant nutrition. Tropical and subtropical agroecosystems. 17 (2): 173-183.
7. Barton JC 2007. Chelation therapy for iron overload. Current gastroenterology reports. 9 (1): 74-82.
8. Bentley R 2006. From miso, sake and shoyu to cosmetics: a century of science for kojic acid. Natural product reports. 23 (6): 1046-1062.
9. Borsari M, et al. 2001. Silybin, a new iron-chelating agent. Journal of inorganic biochemistry. 85 (2-3): 123-129.
10. Clifford MN 2000. Chlorogenic acids and other cinnamates - Nature, occurrence, dietary burden, absorption and metabolism. Journal of the science of food and agriculture. 80 (7): 1033-1043.
11. Das SK, Desaulniers J, Dyck JRB, Kassiri Z & Oudit GY 2016. Resveratrol mediates therapeutic hepatic effects in acquired and genetic murine models of iron-overload. Liver international. 36 (2): 246-257.
12. Das SK, et al. 2015. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy. Scientific reports. 5.
13. Dinda B, et al. 2017. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. European journal of medicinal chemistry. 131: 68-80.
14. Ding M, Bhupathiraju SN, Satija A, Van Dam RM & Hu FB 2014. Long-term coffee consumption and risk of cardiovascular disease: A systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation. 129 (6): 643-659.
15. Dolatabadi JEN, Mokhtarzadeh A, Ghareghoran SM & Dehghan G 2014. Synthesis, characterization and antioxidant property of Quercetin-Tb(III) complex. Advanced pharmaceutical bulletin. 4 (2): 101-104.
16. Fang K, et al. 2015. Effect of environmental factors on the complexation of iron and humic acid. Journal of environmental sciences (China). 27 (C): 188-196.
17. Ferlazzo N, et al. 2016. Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe3+-induced oxidative stress. Environmental toxicology and pharmacology. 43: 248-256.
18. Ferrali M, et al. 1997. Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Letters. 416 (2): 123-129.
19. Gallagher ML 2012. Intake: The Nutrients and Their Metabolism In Krause's food the nutrition care process (ed. L. Mahan, S. Escott-Stump, J. Raymond and M. Krause), pp. 32-135. Elsevier: Canada.
20. Guo R, Wei P & Liu W 2007. Combined antioxidant effects of rutin and Vitamin C in Triton X-100 micelles. Journal of pharmaceutical and biomedical analysis. 43 (4): 1580-1586.
21. Hagag AA, Elfrargy MS, Gazar RA & El-Lateef AEA 2013. Therapeutic value of combined therapy with deferasirox and silymarin on iron overload in children with beta thalassemia. Mediterranean journal of hematology and infectious diseases. 5 (1): 1-7.
22. Hegarty MP, Lee CP, Christie GS, Court RD & Haydock KP 1979. The goitrogen 3-hydroxy-4(1H)-pyridone, a ruminal metabolite from Leucaena leucocephala: effects in mice and rats. Australian journal of biological sciences. 32 (1): 27-40.
23. Hershko C 2010. Pathogenesis and management of iron toxicity in thalassemia. In Annals of the New York Academy of Sciences, pp. 1-9.
24. Hershko C, et al. 2003. Objectives and methods of iron chelation therapy. Bioinorganic chemistry and applications. 1 (2): 151-168.
25. Huayhuaz JAA, et al. 2017. Desferrioxamine and desferrioxamine-caffeine as carriers of aluminum and gallium to microbes via the Trojan Horse Effect. Journal of trace elements in medicine and biology. 41: 16-22.
26. Ikeda H, Kimura Y, Masaki M & Iwahashi H 2011. Caffeic acid inhibits the formation of 1-hydroxyethyl radical in the reaction mixture of rat liver microsomes with ethanol partly through its metal chelating activity. Journal of clinical biochemistry and nutrition. 48 (3): 187-193.
27. Imam MU, Zhang S, Ma J, Wang H & Wang F 2017. Antioxidants mediate both iron homeostasis and oxidative stress. Nutrients. 9 (7).
28. Inamori Y, et al. 1997. Biological activity of purpurogallin. Bioscience, biotechnology and biochemistry. 61 (5): 890-892.
29. Jayakumar T, et al. 2013. Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo. Evidence-based complementary and alternative medicine. 2013.
30. Jiao Y, et al. 2009. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 113 (2): 462-469.
31. Kontoghiorghe CN, Kolnagou A & Kontoghiorghes GJ 2015. Phytochelators intended for clinical use in iron overload, other diseases of iron imbalance and free radical pathology. Molecules. 20 (11): 20841-20872.
32. Kontoghiorghes GJ 1988. Structure/red blood cell permeability. Activity of iron(III) chelator complexes. Inorganica chimica acta. 151 (2): 101-106.
33. Kontoghiorghes GJ 1990a. Chelators affecting iron absorption in mice. Arzneimittel-Forschung. 40 (12): 1332-1335.
34. Kontoghiorghes GJ 1990b. Chelators affecting iron absorption in mice. Arzneimittel-Forschung/Drug Research. 40 (12): 1332-1335.
35. Kontoghiorghes GJ, et al. 1987. Effective chelation of iron in β thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. British medical journal 295 (6612): 1509-1512.
36. Kontoghiorghes GJ, Barr J, Nortey P & Sheppard L 1993. Selection of a new generation of orally active α-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload. American journal of hematology. 42 (4): 340-349.
37. Kontoghiorghes GJ & Evans RW 1985. Site specificity of iron removal from transferrin by alpha-ketohydroxypyridine chelators. FEBS Lett. 189 (1): 141-144.
38. Kontoghiorghes GJ, Jackson MJ & Lunec J 1986a. In vitro screening of iron chelators using models of free radical damage. Free radical research. 2 (1-2): 115-124.
39. Kontoghiorghes GJ, Jackson MJ & Lunec J 1986b. In vitro screening of iron chelators using models of free radical damage. Free radical research communications. 2 (1-2): 115-124.
40. Kontoghiorghes GJ, Pattichis K, Neocleous K & Kolnagou A 2004. The design and development of deferiprone (L1) and other iron chelators for clinical use: Targeting methods and application prospects. Current medicinal chemistry. 11 (16): 2161-2183.
41. Korkina LG & Afanas'ev IB 1997. Antioxidant and chelating properties of flavonoids. Advances in pharmacology. 38: 151-163.
42. Kotyzova D, Eybl V, Koutensky J, Brtko J & Glattre E 2004. Effects of kojic acid on oxidative damage and on iron and trace element level in iron-overloaded mice and rats. Central European journal of public health. 12 Suppl: S41-44.
43. Leopoldini M, Russo N, Chiodo S & Toscano M 2006. Iron chelation by the powerful antioxidant flavonoid quercetin. Journal of agricultural and food chemistry. 54 (17): 6343-6351.
44. Lesjak M, et al. 2014. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS ONE. 9 (7).
45. Loguercio C & Festi D 2011. Silybin and the liver: From basic research to clinical practice. World journal of gastroenterology. 17 (18): 2288-2301.
46. Ma Q, Kim EY, Lindsay EA & Han O 2011. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in a Dose-Dependent Manner in Human Intestinal Caco-2 Cells. Journal of food science. 76 (5): H143-H150.
47. Matsui Y, Tanaka Y & Iwahashi H 2017. A comparative study of the inhibitory effects by caffeic acid, catechins and their related compounds on the generation of radicals in the reaction mixture of linoleic acid with iron ions. Journal of clinical biochemistry and nutrition. 60 (3): 162-168.
48. Mazzone G, Malaj N, Russo N & Toscano M 2013. Density functional study of the antioxidant activity of some recently synthesized resveratrol analogues. Food chemistry. 141 (3): 2017-2024.
49. Moayedi B, et al. 2013. A randomized double-blind, placebo-controlled study of therapeutic effects of silymarin in beta-thalassemia major patients receiving desferrioxamine. European journal of haematology. 90 (3): 202-209.
50. Mohammadpour M, Behjati M, Sadeghi A & Fassihi A 2013. Wound healing by topical application of antioxidant iron chelators: Kojic acid and deferiprone. International wound journal. 10 (3): 260-264.
51. Mostert LJ, Van Dorst JALM, Koster JF, van Eijk HG & Kontoghiorghes GJ 1987. Free radical and cytotoxic effects of chelators and their iron complexes in the hepatocyte. Free radical research. 3 (6): 379-388.
52. Nakano H, et al. 2006. Human metallothionein gene expression is upregulated by β-thujaplicin: Possible involvement of protein kinase C and reactive oxygen species. Biological and pharmaceutical bulletin. 29 (1): 55-59.
53. Namba K & Murata Y 2010. Toward mechanistic elucidation of iron acquisition in barley: Efficient synthesis of mugineic acids and their transport activities. Chemical record. 10 (2): 140-150.
54. Niu Q, et al. 2016. Proanthocyanidin Protects Human Embryo Hepatocytes from Fluoride-Induced Oxidative Stress by Regulating Iron Metabolism. Biological trace element research. 169 (2): 174-179.
55. Nurchi VM, et al. 2011. Kojic acid derivatives as powerful chelators for iron(III) and aluminium(III). Dalton transactions. 40 (22): 5984-5998.
56. Ochiai B, Kamiya M & Endo T 2012. Synthesis and Fe(III)-complexation ability of polyurethane bearing kojic acid skeleton in the main chain prepared by polyaddition of aliphatic hydroxyl groups without protection of phenolic hydroxyl groups. Journal of polymer science, Part A: Polymer chemistry. 50 (17): 3493-3498.
57. Ohta Y, et al. 1997. Comparative study of oral and parenteral administration of sho-saiko-to (xiao-chaihu-tang) extract on d-galactosamine-induced liver injury in rats. American journal of Chinese medicine. 25 (3-4): 333-342.
58. Oke-Altuntas F, Aslim B, Duman H & Kartal M 2016. Comparative evaluation of total phenolic/carotenoid contents, chlorogenic acid/rutin profiles, and antioxidant properties of two prangos species (P. Uechtritzii And P. Pabularia). International journal of pharmacy and pharmaceutical sciences. 8 (1): 284-288.
59. Olabinri BM, Eniyansoro OO, Okoronkwo CO, Olabinri PF & Olaleye MT 2010. Evaluation of chelating ability of aqueous extract of Tetracarpidium conophorum (African walnut) in vitro. International journal of applied research in natural products. 3 (3): 13-18.
60. Perron NR & Brumaghim JL 2009. A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell biochemistry and biophysics. 53 (2): 75-100.
61. Pole SN 2006. Wheat grass juice in thalassemia. Indian pediatrics. 43 (1): 79-80.
62. Saniewski M, Saniewska A & Kanlayanarat S 2007. Biological activities of tropolone and hinokitiol: The tools in plant physiology and their practical use. In Acta horticulturae, pp. 133-142.
63. Shander A, Cappellini MD & Goodnough LT 2009. Iron overload and toxicity: The hidden risk of multiple blood transfusions. Vox sanguinis. 97 (3): 185-197.
64. Shimoi K, et al. 1997. Protection by αG-Rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate. Japanese journal of cancer research. 88 (5): 453-460.
65. Srichairatanakool S, et al. 2006. Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. Hemoglobin. 30 (2): 311-327.
66. Srichairatanakool S, Thephinlap C, Phisalaphong C, Porter JB & Fucharoen S 2007. Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma. Medicinal chemistry. 3 (5): 469-474.
67. Tang Y, et al. 2014. Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway. Journal of nutritional biochemistry. 25 (6): 675-682.
68. Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB & Srichairatanakool S 2009. Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice. Medicinal chemistry. 5 (5): 474-482.
69. Ullmann U, Haller J, Bakker GCM, Brink EJ & Weber P 2005. Epigallocatechin gallate (EGCG) (TEAVIGO™) does not impair nonhaem-iron absorption in man. Phytomedicine. 12 (6-7): 410-415.
70. Van Schaik JWJ, Persson I, Kleja DB & Gustafsson JP 2008. EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. Environmental science and technology. 42 (7): 2367-2373.
71. Weber G, Von Wirén N & Hayen H 2008. Investigation of ascorbate-mediated iron release from ferric phytosiderophores in the presence of nicotianamine. BioMetals. 21 (5): 503-513.
72. Yang CS, Chen G & Wu Q 2014. Recent scientific studies of a traditional Chinese medicine, tea, on prevention of chronic diseases. Journal of traditional and complementary medicine. 4 (1): 17-23.
73. Yang R & Van Den Berg CMG 2009. Metal complexation by humic substances in seawater. Environmental science and technology. 43 (19): 7192-7197.
74. Yoshino M & Murakami K 1998. Interaction of iron with polyphenolic compounds: Application to antioxidant characterization. Analytical biochemistry. 257 (1): 40-44.
75. Zhang Y, Gao Z, Liu J & Xu Z 2011. Protective effects of baicalin and quercetin on an iron-overloaded mouse: Comparison of liver, kidney and heart tissues. Natural product research. 25 (12): 1150-1160.
76. Zhang Y, Li H, Zhao Y & Gao Z 2006. Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury. European journal of pharmacology. 535 (1-3): 263-269.
77. Zhao L, et al. 2015. Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character. Journal of nutritional biochemistry. 26 (11): 1174-1182.
78. Zhao Y, Li H, Gao Z & Xu H 2005. Effects of dietary baicalin supplementation on iron overload-induced mouse liver oxidative injury. European journal of pharmacology. 509 (2-3): 195-200.
79. Zijp IM, Korver O & Tijburg LBM 2000. Effect of tea and other dietary factors on iron absorption. Critical reviews in food science and nutrition. 40 (5): 371-398.

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