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
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Hydrophilic Phytochelators in Iron Overload Condition
Zohreh Sajadi Hezaveh; MSc1 & Farzad Shidfar; PhD*1
1 Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
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.
Keywords: Iron overload; Iron chelation; Iron chelator; Antioxidant, Flavonoid; Polyphenol.
Article history:
Received: 7 Apr 2018
Revised: 18 Jun 2018
Accepted: 14 Sep 2018
*Corresponding author
Faculty of Para- medicine, Iran University of Medical Sciences, before the Chamran  intersection, East Hemmat highway, Tehran, Iran.
Postal code: 1449614535
Tel: 0+98- 123082922
The important role of iron in human body is undeniable. Iron is an essential cofactor for hundreds of proteins and enzymes that participates in oxidation and reduction reactions. It is also involved in red blood cell function, myoglobin activity, immune function, cognitive performance, brain function, as well as function and synthesis of neurotransmitters. Therefore, iron deficiency can cause multiple organ malfunctions. However, iron overload can be as destructive and dangerous as its deficiency (Barton, 2007).
Hemochromatosis is a hereditary condition with excessive iron absorption. Hemosiderosis is an iron storage condition that develops in individuals who consume abnormally large amounts of iron or in those with a genetic defect resulting in excessive iron absorption. Iron overload is also observed
in thalassemia, cycle cell disease, and myelodysplasia, which is due to blood transfusion therapy transmitting 200 to 250 mg of iron to the patient's body per unit. Iron overload is attributed to a distinct gene that favors excessive iron absorption and absorbs the iron that exists in the diet. In other words, these patients experience severe iron toxicity (Gallagher, 2012).
Iron must be bound to proteins such as ferritin, hemosiderin, and transferrin to prevent its destructive effects, but by increase in the amount of iron, the liver fails to produce enough protein to store iron. Therefore, excessive free iron will be produced as a result. Since body cannot deal with this large amount of excessive iron, it deposits iron into organs such as the heart, liver, and endocrine organs, which leads to dysfunction of these organs. The consequences of this disease represent as liver dysfunction, cardiomyopathy, diabetes, and even death. Chemically, free iron is a highly reactive element that can interact with oxygen to form intermediates with the potential of damaging cell membranes, degrading DNA, oxidating LDL cholesterol, and finally damaging the cardiovascular system. It also helps to generate excessive amounts of free radicals that attack cellular molecules and develop carcinogenic molecules within cells (Hershko et al., 2003, Shander et al., 2009).
Chelation therapy removes excessive iron effectively. Desferrioxamine (DFO), deferiprone (L1), and deferasirox (1CL670) are currently available chelating drugs, which bind with Fe+ molecules from organs and eliminate them through urine or feces. However, regardless of their iron-removing characteristic, these drugs' serious adverse effects overshadow the patient's life. Desferrioxamine causes reactions at infusion
sites, inducing hearing, vision, growth, and
skeletal abnormalities, and Yersinia infection. Agranulocytosis, transient neutropenia, arthralgia, mild gastrointestinal symptoms, and mild aminotransferase elevation are caused by L1. Deferasirox induces skin rash, elevation of serum creatinine, mild gastrointestinal symptom, mild aminotransferase elevations, as well as hearing and vision abnormalities. Another problem of using such drugs is that they remove iron as well as other two valence metals such as zinc and cause micromineral deficiency (Barton, 2007).
Recently, biochemical studies highlighted the possible iron-chelating properties of flavonoids and polyphenolic compounds with at least two iron binding sites. These flavonoids are divided into two categories of lipophilic and hydrophilic chelators. Lipophilic chelators represent the opposite effect to L1 and DFO, increase iron absorption, minimize iron excretion, and increase deposition of excess iron in tissues. Therefore, they are considered to be a possible treatment for iron deficiency anemia. On the other hand, hydrophilic chelators are different. They eliminate excessive iron and decrease iron absorption in addition to exerting antioxidant and anti-inflammatory activity without causing adverse effects and other metal deficiencies (Kontoghiorghe et al., 2015). The combination of synthetic iron chelators with these antioxidants or even replacing them with natural chelators would be a possible treatment for iron overload. Here are some natural hydrophilic iron chelators:
Quercetin is a member of flavones that mainly exists in apples, onions, tea, red wines, and berries. As experimental studies demonstrated, it possesses numerous beneficial effects on human health, many of which are correlated to its antioxidant capability. Quercetin can scavenge free radical species and has synergistic effects with enzymes and physiological antioxidants (Dolatabadi et al., 2014). The catechol moiety is a possible site on Quercetin for the iron chelation and the high binding energy values indicate that Quercetin is a powerful chelating agent that can sequester iron to prevent its involvement in oxidation reaction (Leopoldini et al., 2006).
Studies in iron-dextran induced iron overloaded mice showed that the injected Quercetin could reduce the hepatic iron overload, decrease serum ferritin, and increase the