Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress

Nutrients - Tập 9 Số 7 - Trang 671
Mustapha Umar Imam1, Shenshen Zhang1, Jifei Ma1, Hao Wang2,1, Fudi Wang2,1
1Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
2Department of Nutrition, Nutrition Discovery Innovation Center, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310058, China

Tóm tắt

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions.

Từ khóa


Tài liệu tham khảo

Kohgo, 2008, Body iron metabolism and pathophysiology of iron overload, Int. J. Hematol., 88, 7, 10.1007/s12185-008-0120-5

Beard, 1998, Iron metabolism: A comprehensive review, Nutr. Rev., 54, 295, 10.1111/j.1753-4887.1996.tb03794.x

Papanikolaou, 2005, Iron metabolism and toxicity, Toxicol. Appl. Pharm., 202, 199, 10.1016/j.taap.2004.06.021

Bresgen, 2015, Oxidative stress and the homeodynamics of iron metabolism, Biomolecules, 5, 808, 10.3390/biom5020808

Emerit, 2001, Iron metabolism, free radicals, and oxidative injury, Biomed. Pharmacother., 55, 333, 10.1016/S0753-3322(01)00068-3

Rouault, 2008, Iron–sulfur cluster biogenesis and human disease, Trends Genet., 24, 398, 10.1016/j.tig.2008.05.008

Beinert, 1997, Iron-sulfur clusters: Nature’s modular, multipurpose structures, Science, 277, 653, 10.1126/science.277.5326.653

Oexle, 1999, Iron-dependent changes in cellular energy metabolism: Influence on citric acid cycle and oxidative phosphorylation, Biochim. Biophys. Acta, 1413, 99, 10.1016/S0005-2728(99)00088-2

Gropper, S.S., and Smith, J.L. (2013). Advanced Nutrition and Human Metabolism, Wadsworth. [6th ed.].

1999, Animal-and plant-food-based diets and iron status: Benefits and costs, Proc. Nutr. Soc., 58, 235, 10.1017/S0029665199000324

Camacho, 2002, Iron deficiency and iron fortified foods—A review, Food Res. Int., 35, 225, 10.1016/S0963-9969(01)00189-2

Wang, 2011, Regulation of cellular iron metabolism, Biochem. J., 434, 365, 10.1042/BJ20101825

West, 2000, Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE, J. Biol. Chem., 275, 38135, 10.1074/jbc.C000664200

Kumar, 2012, Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor, Int. J. Biochem. Cell Biol., 44, 189, 10.1016/j.biocel.2011.10.016

Sheokand, 2013, Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition, Biochim. Biophys. Acta, 1830, 3816, 10.1016/j.bbagen.2013.03.019

Hentze, 2010, Two to tango: Regulation of Mammalian iron metabolism, Cell, 142, 24, 10.1016/j.cell.2010.06.028

Lane, 2015, Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease, Biochim. Biophys. Acta, 1853, 1130, 10.1016/j.bbamcr.2015.01.021

Ganz, 2005, Cellular iron: Ferroportin is the only way out, Cell Metab., 1, 155, 10.1016/j.cmet.2005.02.005

Cook, 1974, Serum ferritin as a measure of iron stores in normal subjects, Am. J. Clin. Nutr., 27, 681, 10.1093/ajcn/27.7.681

Theil, 2012, Ferritin protein nanocages—The story, Nanotechnol. Percept., 8, 7, 10.4024/N03TH12A.ntp.08.01

Theil, 1987, Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms, Annu. Rev. Biochem., 56, 289, 10.1146/annurev.bi.56.070187.001445

Zhang, 2010, Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit, Antioxid. Redox Signal., 13, 999, 10.1089/ars.2010.3129

Roeser, 1970, The role of ceruloplasmin in iron metabolism, J. Clin. Investig., 49, 2408, 10.1172/JCI106460

Nemeth, 2006, Regulation of iron metabolism by hepcidin, Annu. Rev. Nutr., 26, 323, 10.1146/annurev.nutr.26.061505.111303

Ganz, 2012, Hepcidin and iron homeostasis, Biochim. Biophys. Acta, 1823, 1434, 10.1016/j.bbamcr.2012.01.014

Schmidt, 2015, Regulation of iron metabolism by hepcidin under conditions of inflammation, J. Biol. Chem., 290, 18975, 10.1074/jbc.R115.650150

Ganz, 2003, Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation, Blood, 102, 783, 10.1182/blood-2003-03-0672

Pantopoulos, 2004, Iron metabolism and the IRE/IRP regulatory system: An update, Ann. N. Y. Acad. Sci., 1012, 1, 10.1196/annals.1306.001

Laurent, 2014, Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: Opportunities and challenges, Expert Opin. Drug Deliv., 11, 1449, 10.1517/17425247.2014.924501

Cabantchik, 2002, Intracellular and extracellular labile iron pools, Adv. Exp. Med. Biol., 509, 55, 10.1007/978-1-4615-0593-8_4

Finney, 2003, Transition metal speciation in the cell: Insights from the chemistry of metal ion receptors, Science, 300, 931, 10.1126/science.1085049

Philpott, 2014, Special delivery: Distributing iron in the cytosol of mammalian cells, Front. Pharmacol., 5, 173, 10.3389/fphar.2014.00173

Halliwell, 1994, Free radicals, antioxidants, and human disease curiosity, cause, or consequence?, Lancet, 344, 721, 10.1016/S0140-6736(94)92211-X

Valko, 2007, Free radicals and antioxidants in normal physiological functions and human disease, Int. J. Biochem. Cell Biol., 39, 44, 10.1016/j.biocel.2006.07.001

Mylonas, 1999, Lipid peroxidation and tissue damage, In Vivo (Athens, Greece), 13, 295

Crichton, 2002, Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells, J. Inorg. Biochem., 91, 9, 10.1016/S0162-0134(02)00461-0

Camaschella, 2015, Iron deficiency anemia, N. Engl. J. Med., 372, 1832, 10.1056/NEJMra1401038

Leung, 2000, Iron deficiency anemia, Adv. Pediatr., 48, 385, 10.1016/S0065-3101(23)00084-1

Tsai, 2014, Iron deficiency anemia in predominantly breastfed young children, Pediatr. Neonatol., 55, 466, 10.1016/j.pedneo.2014.02.005

Allen, 2000, Anemia and iron deficiency: Effects on pregnancy outcome, Am. J. Clin. Nutr., 71, 1280s, 10.1093/ajcn/71.5.1280s

Cassat, 2013, Iron in infection and immunity, Cell Host Microbe, 13, 509, 10.1016/j.chom.2013.04.010

Grune, 2000, Oxidative stress in anemia, Clin. Nephrol., 53, S18

Fibach, 2008, The role of oxidative stress in hemolytic anemia, Curr. Mol. Med., 8, 609, 10.2174/156652408786241384

Cadet, 2003, Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis, Hum. Mol. Genet., 12, 2241, 10.1093/hmg/ddg225

Kruszewski, 2003, Labile iron pool: The main determinant of cellular response to oxidative stress, Mutat. Res., 531, 81, 10.1016/j.mrfmmm.2003.08.004

Dixon, 2014, The role of iron and reactive oxygen species in cell death, Nat. Chem. Biol., 10, 9, 10.1038/nchembio.1416

Lunova, 2014, Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload, J. Hepatol., 61, 633, 10.1016/j.jhep.2014.04.034

Fortes, 2012, Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production, Blood, 119, 2368, 10.1182/blood-2011-08-375303

Roy, 2012, Bid-induced mitochondrial membrane permeabilization waves propagated by local reactive oxygen species (ROS) signaling, Proc. Natl. Acad. Sci. USA, 109, 4497, 10.1073/pnas.1118244109

Dixon, 2012, Ferroptosis: An iron-dependent form of nonapoptotic cell death, Cell, 149, 1060, 10.1016/j.cell.2012.03.042

Yang, 2014, Regulation of ferroptotic cancer cell death by GPX4, Cell, 156, 317, 10.1016/j.cell.2013.12.010

Shimada, 2016, Cell-line selectivity improves the predictive power of pharmacogenomicanalyses and helps identify NADPH as biomarker for ferroptosissensitivity, Cell Chem. Biol., 23, 225, 10.1016/j.chembiol.2015.11.016

Jiang, 2015, Ferroptosis as a p53-mediated activity during tumour suppression, Nature, 520, 57, 10.1038/nature14344

Wang, H., An, P., Xie, E., Wu, Q., Fang, X., Gao, H., Zhang, Z., Li, Y., Wang, X., and Zhang, J. (2017). Characterization of ferroptosis in murine models of hemochromatosis. Hepatology.

Kwon, 2015, Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death, Oncotarget, 6, 24393, 10.18632/oncotarget.5162

Gao, 2015, Glutaminolysis and transferrin regulate ferroptosis, Mol. Cell, 59, 298, 10.1016/j.molcel.2015.06.011

Hou, 2016, Autophagy promotes ferroptosis by degradation of ferritin, Autophagy, 12, 1425, 10.1080/15548627.2016.1187366

Zelko, 2002, Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression, Free Radic. Biol. Med., 33, 337, 10.1016/S0891-5849(02)00905-X

Wu, 2004, Glutathione metabolism and its implications for health, J. Nutr., 134, 489, 10.1093/jn/134.3.489

Chae, 1999, Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin, Diabetes Res. Clin. Pract., 45, 101, 10.1016/S0168-8227(99)00037-6

Willcox, 2010, Antioxidants and Prevention of Chronic Disease, Crit. Rev. Food Sci. Nutr., 4, 275

Temple, 2000, Antioxidants and disease: More questions than answers, Nutr. Res., 20, 449, 10.1016/S0271-5317(00)00138-X

Sripetchwandee, J., Pipatpiboon, N., Chattipakorn, N., and Chattipakorn, S. (2014). Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity. PLoS ONE, 9.

Wongjaikam, S., Kumfu, S., Khamseekaew, J., Sripetchwandee, J., Srichairatanakool, S., Fucharoen, S., and Chattipakorn, N. (2016). Combined iron chelator and antioxidant exerted greater efficacy on cardioprotection than monotherapy in iron-overloaded rats. PLoS ONE, 11.

Galati, 2004, Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties, Free Radic. Biol. Med., 37, 287, 10.1016/j.freeradbiomed.2004.04.034

Ferlazzo, 2016, Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe3+—Induced oxidative stress, Environ. Toxicol. Pharmacol., 43, 248, 10.1016/j.etap.2016.03.005

Ma, 2011, Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 Cells, J. Food Sci., 76, H143, 10.1111/j.1750-3841.2011.02184.x

Shin, 2016, Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2, Int. J. Mol. Med., 38, 1075, 10.3892/ijmm.2016.2694

Jiao, 2009, Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator, Blood, 113, 462, 10.1182/blood-2008-05-155952

Zhong, 2016, Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling, Biomed. Pharmacother., 83, 302, 10.1016/j.biopha.2016.06.036

Tang, 2014, Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway, J. Nutr. Biochem., 25, 675, 10.1016/j.jnutbio.2014.02.009

Mu, 2016, The dietary flavonoid myricetin regulates iron homeostasis by suppressing hepcidin expression, J. Nutr. Biochem., 30, 53, 10.1016/j.jnutbio.2015.10.015

Zhen, 2013, The small molecule, genistein, increases hepcidin expression in human hepatocytes, Hepatology, 58, 1315, 10.1002/hep.26490

Reisi, 2015, Evaluating the safety and efficacy of silymarin in β-thalassemia patients: A review, Hemoglobin, 39, 75, 10.3109/03630269.2014.1003224

Qiao, Y., He, H., Zhang, Z., Liao, Z., Yin, D., Liu, D., and He, M. (2016). Long-term sodium ferulate supplementation scavenges oxygen radicals and reverses liver damage induced by iron overloading. Molecules, 21.

Das, 2014, Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy, Sci. Rep., 5, 18132, 10.1038/srep18132

Basta, 2014, Effect of supplementation with chokeberry juice on the inflammatory status and markers of iron metabolism in rowers, J. Int. Soc. Sports Nutr., 11, 48, 10.1186/s12970-014-0048-5

Layrisse, 1997, Vitamin A and β-carotene can improve nonheme iron absorption from rice, wheat and corn by humans, J. Nutr., 128, 646

Citelli, 2012, Vitamin A modulates the expression of genes involved in iron bioavailability, Biol. Trace Elem. Res., 149, 64, 10.1007/s12011-012-9397-6

Katz, 2015, β-Carotene can reverse dysregulation of iron protein in an in vitro model of inflammation, Immunol. Res., 61, 70, 10.1007/s12026-014-8570-8

Chiu, 2012, Vitamin C affects the expression of hepcidin and erythropoietin receptor in HepG2 cells, J. Ren. Nutr., 22, 373, 10.1053/j.jrn.2011.09.007

Fustinoni-Reis, A.M., Arruda, S.F., Dourado, L.P., da Cunha, M.S., and Siqueira, E. (2016). Tucum-Do-Cerrado (Bactrissetosa Mart.) consumption modulates iron homeostasis and prevents iron-induced oxidative stress in the rat liver. Nutrients, 8.

Perez, 2009, Iron-binding and anti-Fenton properties of baicalein and baicalin, J. Inorg. Biochem., 103, 326, 10.1016/j.jinorgbio.2008.11.003

Guan, 2013, Screening identifies the Chinese medicinal plant Caulis Spatholobi as an effective HAMP expression inhibitor, J. Nutr., 143, 1061, 10.3945/jn.113.174201

Zhang, 2015, Astragalus polysaccharide suppresses palmitate-induced apoptosis in human cardiac myocytes: The role of Nrf1 and antioxidant response, Int. J. Clin. Exp. Pathol., 8, 2515

Ren, 2016, Astragalus polysaccharide upregulateshepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase, Biochem. Biophys. Res. Commun., 472, 163, 10.1016/j.bbrc.2016.02.088

Zhuang, 2016, Polysaccharide from Angelica sinensis protects chondrocytes from H2O2-induced apoptosis through its antioxidant effects in vitro, Int. J. Biol. Macromol., 87, 322, 10.1016/j.ijbiomac.2016.02.031

Cheng, 2016, The effects of polysaccharides from the root of Angelica sinensis on tumor growth and iron metabolism in H22-bearing mice, Food Funct., 7, 1033, 10.1039/C5FO00855G

Scherbinina, 2012, Effect of exogenous antioxidants on erythrocyte redox status and hepcidin content in disorders of iron metabolism regulation, Biochemistry, 6, 338

Nguyen, 2009, The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress, J. Biol. Chem., 284, 13291, 10.1074/jbc.R900010200

Vauzour, 2010, Polyphenols and human health: prevention of disease and mechanisms of action, Nutrients, 2, 1106, 10.3390/nu2111106

Pandey, 2009, Plant polyphenols as dietary antioxidants in human health and disease, Oxid. Med. Cell. Longev., 2, 270, 10.4161/oxim.2.5.9498

Niu, 2016, Proanthocyanidin protects human embryo hepatocytes from fluoride-induced oxidative stress by regulating iron metabolism, Biol. Trace Elem. Res., 169, 174, 10.1007/s12011-015-0409-1

Cao, 1997, Antioxidant and prooxidant behavior of flavonoids: Structure-activity relationships, Free Radic. Biol. Med., 22, 749, 10.1016/S0891-5849(96)00351-6

Zhao, 2016, Protective Effects of genistein and puerarin against chronic alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, J. Agric. Food Chem., 64, 7291, 10.1021/acs.jafc.6b02907

Rathee, 2009, Mechanism of action of flavonoids as anti-inflammatory agents: A review, Inflamm. Allergy Drug Targets, 8, 229, 10.2174/187152809788681029

Bayele, 2015, Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption, Free Radic. Biol. Med., 89, 1192, 10.1016/j.freeradbiomed.2015.11.001

Oboh, 2016, Quercetin and its role in chronic diseases, Adv. Exp. Med. Biol., 929, 377, 10.1007/978-3-319-41342-6_17

Kumar, 2014, Potential applications of ferulic acid from natural sources, Biotechnol. Rep., 4, 86, 10.1016/j.btre.2014.09.002

Bradamante, 2004, Cardiovascular protective effects of resveratrol, Cardiovasc. Drug Rev., 22, 169, 10.1111/j.1527-3466.2004.tb00139.x

Tang, 2014, Resveratrol and cardiovascular health—Promising therapeutic or hopeless illusion?, Pharmacol. Res., 90, 88, 10.1016/j.phrs.2014.08.001

Wu, 2004, Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia and Sambucus and their antioxidant capacity, J. Agric. Food Chem., 52, 7846, 10.1021/jf0486850

Taheri, 2013, Underutilized chokeberry (Aroniamelanocarpa, Aroniaarbutifolia, Aroniaprunifolia) accessions are rich sources of anthocyanins, flavonoids, hydroxycinnamic acids, and proanthocyanidins, J. Agric. Food Chem., 61, 8581, 10.1021/jf402449q

McDowell, L.R., Wilkinson, N., Madison, R., and Felix, T.L. (2007). Vitamins and minerals functioning as antioxidants with supplementation considerations. Florida Ruminant Nutrition Symposium, Best Western Gateway Grand.

Kennedy, 1992, Peroxyl radical scavenging by beta-carotene in lipid bilayers. Effect of oxygen partial pressure, J. Biol. Chem., 267, 4658, 10.1016/S0021-9258(18)42884-0

Ramalho, 2008, Critical analysis of Brazilian studies about vitamin A deficiency in maternal child group, Rev. Paul. Pediatr., 26, 392, 10.1590/S0103-05822008000400014

Chew, 1998, Hematological effect of supplementing anemic children with vitamin A alone and in combinations with iron, Am. J. Clin. Nutr., 48, 595

Bloem, 1990, Vitamin A intervention: Short-term effects of a single, oral, massive dose on iron metabolism, Am. J. Clin. Nutr., 51, 76, 10.1093/ajcn/51.1.76

Kelleher, 2005, Low vitamin A intake affects milk iron and iron transporters in rat mammary gland and liver, J. Nutr., 135, 27, 10.1093/jn/135.1.27

Imam, 2016, Are bioactive-rich fractions functionally richer?, Crit. Rev. Biotechnol., 36, 585, 10.3109/07388551.2014.995586