Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2015, Article ID 516740, 12 pages
http://dx.doi.org/10.1155/2015/516740
Review Article

The Utility of Iron Chelators in the Management of Inflammatory Disorders

1Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, 5850 College St., Halifax, NS, Canada B3H 1X5
2Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS, Canada B3H 1X5
3Department of Pharmacology, Dalhousie University, 5850 College St., Halifax, NS, Canada B3H 1X5
4Department of Pharmacy, East West University, Plot No. A/2, Jahurul Islam City, Aftabnagar, Dhaka 1219, Bangladesh
5Department of Pathology, Dalhousie University, 5850 College St., Halifax, NS, Canada B3H 1X5
6Department of Physiology, Faculty of Medicine, Cairo University, 1 Al-Saray St., Cairo 11559, Egypt
7Chelation Partners Inc., 1411 Oxford St., Halifax, NS, Canada B3H 3Z1

Received 20 June 2014; Revised 1 September 2014; Accepted 1 September 2014

Academic Editor: Yung-Hsiang Chen

Copyright © 2015 C. Lehmann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Wessling-Resnick, “Iron homeostasis and the inflammatory response,” Annual Review of Nutrition, vol. 30, pp. 105–122, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. D. B. Kell, “Iron behaving badly: Inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases,” BMC Medical Genomics, vol. 2, article 2, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Nairz, D. Haschka, E. Demetz, and G. Weiss, “Iron at the interface of immunity and infection,” Frontiers in Pharmacology, vol. 5, pp. 1–10, 2014. View at Google Scholar
  4. G. E. Cartwright, M. A. Lauritsen, S. Humphreys, P. J. Jones, I. M. Merrill, and M. M. Wintrobe, “The anemia associated with chronic infection,” Science, vol. 103, no. 2664, pp. 72–73, 1946. View at Publisher · View at Google Scholar · View at Scopus
  5. B. K. Fuqua, C. D. Vulpe, and G. J. Anderson, “Intestinal iron absorption,” Journal of Trace Elements in Medicine and Biology, vol. 26, no. 2-3, pp. 115–119, 2012. View at Publisher · View at Google Scholar
  6. M. Domellöf, I. Thorsdottir, and K. Thorstensen, “Health effects of different dietary iron intakes: a systematic literature review for the 5th Nordic Nutrition Recommendations,” Food & Nutrition Research, p. 57, 2013. View at Google Scholar
  7. G. Weiss, “Iron metabolism in the anemia of chronic disease,” Biochimica et Biophysica Acta, vol. 1790, no. 7, pp. 682–693, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Waldvogel-Abramowski, G. Waeber, C. Gassner et al., “Physiology of iron metabolism,” Transfusion Medicine and Hemotherapy, vol. 41, no. 3, pp. 213–221, 2014. View at Publisher · View at Google Scholar
  9. D. M. Frazer and G. J. Anderson, “The regulation of iron transport,” BioFactors, vol. 40, no. 2, pp. 206–214, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. P. A. Sharp, “Intestinal iron absorption: regulation by dietary & systemic factors,” International Journal for Vitamin and Nutrition Research, vol. 80, no. 4-5, pp. 231–242, 2010. View at Publisher · View at Google Scholar
  11. Z. Cheng and Y. Li, “What is responsible for the initiating chemistry of iron-mediated lipid peroxidation: an update,” Chemical Reviews, vol. 107, no. 3, pp. 748–766, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. E. Nemeth and T. Ganz, “The role of hepcidin in iron metabolism,” Acta Haematologica, vol. 122, no. 2-3, pp. 78–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. M. D. Knutson, “Iron-sensing proteins that regulate hepcidin and enteric iron absorption,” Annual Review of Nutrition, vol. 30, pp. 149–171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. I. de Domenico, D. M. Ward, and J. Kaplan, “Hepcidin and ferroportin: the new players in iron metabolism,” Seminars in Liver Disease, vol. 31, no. 3, pp. 272–279, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Mercadel, M. Metzger, J. P. Haymann et al., “The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease,” PLoS ONE, vol. 9, Article ID e99781, 2014. View at Google Scholar
  16. V. Dzikaite, P. Holmström, P. Stål et al., “Regulatory effects of tumor necrosis factor-alpha and interleukin-6 on HAMP expression in iron loaded rat hepatocytes,” Journal of Hepatology, vol. 44, no. 3, pp. 544–551, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. E. Nemeth, M. S. Tuttle, J. Powelson et al., “Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization,” Science, vol. 306, no. 5704, pp. 2090–2093, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. E. Nemeth, E. V. Valore, M. Territo, G. Schiller, A. Lichtenstein, and T. Ganz, “Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein,” Blood, vol. 101, no. 7, pp. 2461–2463, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. C. Peyssonnaux, A. S. Zinkernagel, V. Datta, X. Lauth, R. S. Johnson, and V. Nizet, “TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens,” Blood, vol. 107, no. 9, pp. 3727–3732, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. E. Panieri, V. Gogvadze, E. Norberg, R. Venkatesh, S. Orrenius, and B. Zhivotovsky, “Reactive oxygen species generated in different compartments induce cell death, survival, or senescence,” Free Radical Biology and Medicine, vol. 57, pp. 176–187, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Valko, D. Leibfritz, J. Moncol, M. T. D. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” International Journal of Biochemistry and Cell Biology, vol. 39, no. 1, pp. 44–84, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Kietzmann, “Intracellular redox compartments: mechanisms and significances,” Antioxidants and Redox Signaling, vol. 13, no. 4, pp. 395–398, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. N. K. Tonks, “Redox redux: revisiting PTPs and the control of cell signaling,” Cell, vol. 121, no. 5, pp. 667–670, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. P. C. Dedon and S. R. Tannenbaum, “Reactive nitrogen species in the chemical biology of inflammation,” Archives of Biochemistry and Biophysics, vol. 423, no. 1, pp. 12–22, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. E. Nemeth, S. Rivera, V. Gabayan et al., “IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin,” Journal of Clinical Investigation, vol. 113, no. 9, pp. 1271–1276, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. D. M. Wrighting and N. C. Andrews, “Interleukin-6 induces hepcidin expression through STAT3,” Blood, vol. 108, no. 9, pp. 3204–3209, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Wang, N. Song, H. Jiang, and J. Xie, “Pro-inflammatory cytokines modulate iron regulatory protein 1 expression and iron transportation through reactive oxygen/nitrogen species production in ventral mesencephalic neurons,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1832, no. 5, pp. 618–625, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. P. Urrutia, P. Aguirre, A. Esparza et al., “Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells,” Journal of Neurochemistry, vol. 126, no. 4, pp. 541–549, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Rivera, L. Liu, E. Nemeth, V. Gabayan, O. E. Sorensen, and T. Ganz, “Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia,” Blood, vol. 105, no. 4, pp. 1797–1802, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. S. H. Atkinson, K. A. Rockett, G. Morgan et al., “Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia inWest African children,” Blood, vol. 112, no. 10, pp. 4276–4283, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. N. C. Andrews and P. J. Schmidt, “Iron homeostasis,” Annual Review of Physiology, vol. 69, pp. 69–85, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Xiong, H. She, C. K. Sung, and H. Tsukamoto, “Iron-dependent activation of NF-κB in Kupffer cells: a priming mechanism for alcoholic liver disease,” Alcohol, vol. 30, no. 2, pp. 107–113, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. H. She, S. Xiong, M. Lin, E. Zandi, C. Giulivi, and H. Tsukamoto, “Iron activates NF-κB in Kupffer cells,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 283, no. 3, pp. G719–G726, 2002. View at Google Scholar · View at Scopus
  34. E. Graf, J. R. Mahoney, R. G. Bryant, and J. W. Eaton, “Iron-catalyzed hydroxyl radical formation: dtringent requirement for free iron coordination site,” The Journal of Biological Chemistry, vol. 259, no. 6, pp. 3620–3624, 1984. View at Google Scholar · View at Scopus
  35. P. Aisen, C. Enns, and M. Wessling-Resnick, “Chemistry and biology of eukaryotic iron metabolism,” International Journal of Biochemistry and Cell Biology, vol. 33, no. 10, pp. 940–959, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. G. Perletti, A. Vral, M. C. Patrosso et al., “Prevention and modulation of aminoglycoside ototoxicity (Review),” Molecular Medicine Reports, vol. 1, no. 1, pp. 3–13, 2008. View at Google Scholar · View at Scopus
  37. M. Imbert, M. Bechet, and R. Blondeau, “Comparison of the main siderophores produced by some species of Streptomyces,” Current Microbiology, vol. 31, no. 2, pp. 129–133, 1995. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Ratledge and L. G. Dover, “Iron metabolism in pathogenic bacteria,” Annual Review of Microbiology, vol. 54, pp. 881–941, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. D. H. Howard, “Acquisition, transport, and storage of iron by pathogenic fungi,” Clinical Microbiology Reviews, vol. 12, no. 3, pp. 394–404, 1999. View at Google Scholar · View at Scopus
  40. E. P. Skaar, “The battle for iron between bacterial pathogens and their vertebrate hosts,” PLoS Pathogens, vol. 6, no. 8, Article ID e1000949, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. J. W. Kronstad and M. Caza, “Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans,” Frontiers in Cellular and Infection Microbiology, vol. 4, article 80, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. R. M. Robins-Browne and J. K. Prpic, “Effects of iron and desferrioxamine on infections with Yersinia enterocolitica,” Infection and Immunity, vol. 47, no. 3, pp. 774–779, 1985. View at Google Scholar · View at Scopus
  43. B. E. Holbein and R. Mira de Orduña, “Effect of trace iron levels and iron withdrawal by chelation on the growth of Candida albicans and Candida vini,” FEMS Microbiology Letters, vol. 307, no. 1, pp. 19–24, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. M. G. Miguel, “Antioxidant and anti-inflammatory activities of essential oils: a short review,” Molecules, vol. 15, no. 12, pp. 9252–9287, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Srichairatanakool, C. Thephinlap, C. Phisalaphong, J. B. Porter, and S. Fucharoen, “Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma,” Medicinal Chemistry, vol. 3, no. 5, pp. 469–474, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Thephinlap, C. Phisalaphong, S. Fucharoen, J. B. Porter, and S. Srichairatanakool, “Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice,” Medicinal Chemistry, vol. 5, no. 5, pp. 474–482, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. K. Aayush, N. Wadhwa, and A. Tiwari, “Therapeutic role of natural agents in beta-thalassemia: a review,” Journal of Pharmacy Research, vol. 6, pp. 954–959, 2013. View at Google Scholar
  48. T. P. Kennedy, N. V. Rao, W. Noah et al., “Ibuprofen prevents oxidant lung injury and in vitro lipid peroxidation by chelating iron,” Journal of Clinical Investigation, vol. 86, no. 5, pp. 1565–1573, 1990. View at Publisher · View at Google Scholar · View at Scopus
  49. D. S. Kalinowski and D. R. Richardson, “Future of toxicology—iron chelators and differing modes of action and toxicity: the changing face of iron chelation therapy,” Chemical Research in Toxicology, vol. 20, no. 5, pp. 715–720, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. M. G. Thompson, B. W. Corey, Y. Si, D. W. Craft, and D. V. Zurawski, “Antibacterial activities of iron chelators against common nosocomial pathogens,” Antimicrobial Agents and Chemotherapy, vol. 56, no. 10, pp. 5419–5421, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. K. V. Kowdley, “Iron, hemochromatosis, and hepatocellular carcinoma,” Gastroenterology, vol. 127, pp. S79–S86, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. D. Galaris, V. Skiada, and A. Barbouti, “Redox signaling and cancer: the role of “labile” iron,” Cancer Letters, vol. 266, no. 1, pp. 21–29, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Benhar, D. Engelberg, and A. Levitzki, “ROS, stress-activated kinases and stress signaling in cancer,” EMBO Reports, vol. 3, no. 5, pp. 420–425, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. N. T. V. Le and D. R. Richardson, “The role of iron in cell cycle progression and the proliferation of neoplastic cells,” Biochimica et Biophysica Acta, vol. 1603, no. 1, pp. 31–46, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. R. Sutherland, D. Delia, C. Schneider, R. Newman, J. Kemshead, and M. Greaves, “Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 7, pp. 4515–4519, 1981. View at Publisher · View at Google Scholar · View at Scopus
  56. D. R. Richardson and E. Baker, “The uptake of iron and transferrin by the human malignant melanoma cell,” Biochimica et Biophysica Acta, vol. 1053, no. 1, pp. 1–12, 1990. View at Publisher · View at Google Scholar · View at Scopus
  57. Z. K. Pinnix, L. D. Miller, W. Wang et al., “Ferroportin and iron regulation in breast cancer progression and prognosis,” Science Translational Medicine, vol. 2, no. 43, Article ID 43ra56, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. B. J. Cherayil, “Iron and immunity: immunological consequences of iron deficiency and overload,” Archivum Immunologiae et Therapiae Experimentalis, vol. 58, no. 6, pp. 407–415, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. S. A. Schwartz, A. Hernandez, and B. Mark Evers, “The role of NF-kappaB/IkappaB proteins in cancer: implications for novel treatment strategies,” Surgical Oncology, vol. 8, pp. 143–153, 1999. View at Publisher · View at Google Scholar
  60. Y.-P. Tsai and K.-J. Wu, “Hypoxia-regulated target genes implicated in tumor metastasis,” Journal of Biomedical Science, vol. 19, no. 1, article 102, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. D. R. Richardson, “Therapeutic potential of iron chelators in cancer therapy,” Advances in Experimental Medicine and Biology, vol. 509, pp. 231–249, 2002. View at Google Scholar
  62. M. Ren, R. Rajendran, P. Ning et al., “Zinc supplementation decreases the development of atherosclerosis in rabbits,” Free Radical Biology and Medicine, vol. 41, no. 2, pp. 222–225, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. N. Ishizaka, K. Saito, I. Mori, G. Matsuzaki, M. Ohno, and R. Nagai, “Iron chelation suppresses ferritin upregulation and attenuates vascular dysfunction in the aorta of angiotensin II-infused rats,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 11, pp. 2282–2288, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. O. Gursel, A. E. Kurekci, E. Tascilar et al., “Premature atherosclerosis in children with β-thalassemia major,” Journal of Pediatric Hematology/Oncology, vol. 34, no. 8, pp. 630–634, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Tajima, Y. Ikeda, K. Sawada et al., “Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice,” The American Journal of Physiology—Endocrinology and Metabolism, vol. 302, no. 1, pp. E77–E86, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. Masuda, H. Ichii, and N. D. Vaziri, “At pharmacologically relevant concentrations intravenous iron preparations cause pancreatic beta cell death,” The American Journal of Translational Research, vol. 6, no. 1, pp. 64–70, 2014. View at Google Scholar · View at Scopus
  67. Y. Ikeda, I. Ozono, S. Tajima et al., “Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction,” PLoS ONE, vol. 9, no. 2, Article ID e89355, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Y. Wang, K. Singh, and S. C. Lin, “Glaucoma prevalence and the intake of iron and calcium in a population-based study,” Current Eye Research, vol. 38, no. 10, pp. 1049–1056, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. P. Liu, M. Zhang, M. Shoeb et al., “Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure,” Free Radical Biology and Medicine, vol. 69, pp. 289–299, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. D. Vlahakos, N. Arkadopoulos, G. Kostopanagiotou et al., “Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs,” Artificial Organs, vol. 36, no. 4, pp. 400–408, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. N. Arkadopoulos, D. Vlahakos, G. Kosotopanagiotou et al., “Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure,” Liver Transplantation, vol. 14, no. 8, pp. 1116–1124, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. G. G. Kostopanagiotou, K. A. Kalimeris, N. P. Arkadopoulos et al., “Desferrioxamine attenuates minor lung injury following surgical acute liver failure,” European Respiratory Journal, vol. 33, no. 6, pp. 1429–1436, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Minaiyan, E. Mostaghel, and P. Mahzouni, “Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants,” International Journal of Preventive Medicine, vol. 3, supplement 1, pp. S162–S169, 2012. View at Google Scholar · View at Scopus
  74. P. G. Jamkhande, P. G. Chandak, S. C. Dhawale, S. R. Barde, P. S. Tidke, and R. S. Sakhare, “Therapeutic approaches to drug targets in atherosclerosis,” Saudi Pharmaceutical Journal, vol. 22, no. 3, pp. 179–190, 2014. View at Publisher · View at Google Scholar · View at Scopus
  75. X.-M. Yuan and W. Li, “Iron involvement in multiple signaling pathways of atherosclerosis: a revisited hypothesis,” Current Medicinal Chemistry, vol. 15, no. 21, pp. 2157–2172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. D. E. Ferrara and W. R. Taylor, “Iron chelation and vascular function: in search of the mechanisms,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 11, pp. 2235–2237, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. W. Kerner and J. Brückel, “Definition, classification and diagnosis of diabetes mellitus,” Experimental and Clinical Endocrinology & Diabetes, vol. 122, pp. 384–386, 2014. View at Google Scholar
  78. E. Oliveros, V. K. Somers, O. Sochor, K. Goel, and F. Lopez-Jimenez, “The concept of normal weight obesity,” Progress in Cardiovascular Diseases, vol. 56, no. 4, pp. 426–433, 2014. View at Publisher · View at Google Scholar · View at Scopus
  79. A. B. Farris and R. B. Colvin, “Renal interstitial fibrosis: mechanisms and evaluation,” Current Opinion in Nephrology and Hypertension, vol. 21, no. 3, pp. 289–300, 2012. View at Publisher · View at Google Scholar
  80. I. B. Torres, F. Moreso, E. Sarró, A. Meseguer, and D. Serón, “The interplay between inflammation and fibrosis in kidney transplantation,” BioMed Research International, vol. 2014, Article ID 750602, 9 pages, 2014. View at Publisher · View at Google Scholar
  81. G. Tezel, “Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences,” Progress in Retinal and Eye Research, vol. 25, no. 5, pp. 490–513, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. P. M. C. K. Klouwenberg, D. S. Y. Ong, M. J. M. Bonten, and O. L. Cremer, “Classification of sepsis, severe sepsis and septic shock: The impact of minor variations in data capture and definition of SIRS criteria,” Intensive Care Medicine, vol. 38, no. 5, pp. 811–819, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. E. Kemna, P. Pickkers, E. Nemeth, H. van der Hoeven, and D. Swinkels, “Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS,” Blood, vol. 106, no. 5, pp. 1864–1866, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. B. E. Holbein, “Iron-controlled infection with Neisseria meningitidis in mice,” Infection and Immunity, vol. 29, no. 3, pp. 886–891, 1980. View at Google Scholar · View at Scopus
  85. D. L. Beaumier, M. A. Caldwell, and B. E. Holbein, “Inflammation triggers hypoferremia and de novo synthesis of serum transferrin and ceruloplasmin in mice,” Infection and Immunity, vol. 46, no. 2, pp. 489–494, 1984. View at Google Scholar · View at Scopus
  86. M. L. Kruzel, J. K. Actor, Z. Radak, A. Bacsi, A. Saavedra-Molina, and I. Boldogh, “Lactoferrin decreases LPS-induced mitochondrial dysfunction in cultured cells and in animal endotoxemia model,” Innate Immunity, vol. 16, no. 2, pp. 67–79, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Ritter, A. Reinke, M. Andrades et al., “Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats,” Critical Care Medicine, vol. 32, no. 10, pp. 2079–2083, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. L.-Y. Guan, P.-Y. Fu, P.-D. Li et al., “Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide,” The World Journal of Gastrointestinal Surgery, vol. 6, pp. 122–128, 2014. View at Google Scholar
  89. M. Kruszewski, “The role of labile iron pool in cardiovascular diseases,” Acta Biochimica Polonica, vol. 51, no. 2, pp. 471–480, 2004. View at Google Scholar · View at Scopus
  90. M. S. Paller and B. O. Hedlund, “Role of iron in postischemic renal injury in the rat,” Kidney International, vol. 34, no. 4, pp. 474–480, 1988. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Stamler, S. Y. Wang, D. E. Aguirre, F. W. Sellke, and R. G. Johnson, “Effects of pentastarch-deferoxamine conjugate on lung injury after cardiopulmonary bypass,” Circulation, vol. 94, no. 9, pp. II358–II363, 1996. View at Google Scholar · View at Scopus
  92. T. Ganz and E. Nemeth, “Iron sequestration and anemia of inflammation,” Seminars in Hematology, vol. 46, no. 4, pp. 387–393, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. C. E. Van Iperen, R. J. Kraaijenhagen, D. H. Biesma, Y. Beguin, J. J. M. Marx, and A. van de Wiel, “Iron metabolism and erythropoiesis after surgery,” British Journal of Surgery, vol. 85, no. 1, pp. 41–45, 1998. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Muñoz, J. A. García-Erce, and Á. F. Remacha, “Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis,” Journal of Clinical Pathology, vol. 64, no. 4, pp. 281–286, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. G. Weiss and L. T. Goodnough, “Anemia of chronic disease,” The New England Journal of Medicine, vol. 352, no. 10, pp. 1011–1023, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. K. H. Park, T. Sawada, T. Kosuge et al., “Surgical inflammation induces hepcidin production after abdominal surgery,” World Journal of Surgery, vol. 36, no. 4, pp. 800–806, 2012. View at Publisher · View at Google Scholar · View at Scopus
  97. E. Gaffney-Stomberg and J. P. McClung, “Inflammation and diminished iron status: mechanisms and functional outcomes,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 15, no. 6, pp. 605–613, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Donovan, C. A. Lima, J. L. Pinkus et al., “The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis,” Cell Metabolism, vol. 1, no. 3, pp. 191–200, 2005. View at Publisher · View at Google Scholar · View at Scopus
  99. A. H. Laftah, B. Ramesh, R. J. Simpson et al., “Effect of hepcidin on intestinal iron absorption in mice,” Blood, vol. 103, no. 10, pp. 3940–3944, 2004. View at Publisher · View at Google Scholar · View at Scopus
  100. E. Beutler, “Iron storage disease: facts, fiction and progress,” Blood Cells, Molecules, and Diseases, vol. 39, no. 2, pp. 140–147, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. C. P. Doherty, “Host-pathogen interactions: the role of iron,” Journal of Nutrition, vol. 137, no. 5, pp. 1341–1344, 2007. View at Google Scholar · View at Scopus
  102. M. Cazzola and C. A. Finch, “Iron balance in thalassemia,” Progress in Clinical and Biological Research, vol. 309, pp. 93–100, 1989. View at Google Scholar · View at Scopus
  103. M. J. Pippard, S. T. Callender, G. T. Warner, and D. J. Weatherall, “Iron absorption and loading in β-thalassaemia intermedia,” The Lancet, vol. 2, no. 8147, pp. 819–821, 1979. View at Google Scholar · View at Scopus
  104. P. B. Walter, E. A. Macklin, J. Porter et al., “Inflammation and oxidant-stress in β-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial,” Haematologica, vol. 93, no. 6, pp. 817–825, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. M. D. Scott, J. J. M. van den Berg, T. Repka et al., “Effect of excess α-hemoglobin chains on cellular and membrane oxidation in model β-thalassemic erythrocytes,” Journal of Clinical Investigation, vol. 91, no. 4, pp. 1706–1712, 1993. View at Publisher · View at Google Scholar · View at Scopus
  106. P. C. Adams, A. E. Kertesz, and L. S. Valberg, “Clinical presentation of hemochromatosis: a changing scene,” The American Journal of Medicine, vol. 90, no. 4, pp. 445–449, 1991. View at Publisher · View at Google Scholar · View at Scopus
  107. J.-M. Fernández-Real, W. Ricart-Engel, E. Arroyo et al., “Serum ferritin as a component of the insulin resistance syndrome,” Diabetes Care, vol. 21, no. 1, pp. 62–68, 1998. View at Publisher · View at Google Scholar · View at Scopus
  108. J. Wärnberg and A. Marcos, “Low-grade inflammation and the metabolic syndrome in children and adolescents,” Current Opinion in Lipidology, vol. 19, no. 1, pp. 11–15, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. J. R. Peterson, R. V. Sharma, and R. L. Davisson, “Reactive oxygen species in the neuropathogenesis of hypertension,” Current Hypertension Reports, vol. 8, no. 3, pp. 232–241, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. T.-P. Tuomainen, K. Punnonen, K. Nyyssönen, and J. T. Salonen, “Association between body iron stores and the risk of acute myocardial infarction in men,” Circulation, vol. 97, no. 15, pp. 1461–1466, 1998. View at Publisher · View at Google Scholar · View at Scopus
  111. G. J. Brewer, “Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease,” Experimental Biology and Medicine, vol. 232, no. 2, pp. 323–335, 2007. View at Google Scholar · View at Scopus
  112. A. Sola, H. Peng, M. Rogido, and T.-C. Wen, “Animal models of neonatal stroke and response to erythropoietin and cardiotrophin-1,” International Journal of Developmental Neuroscience, vol. 26, no. 1, pp. 27–35, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. K. Jellinger, W. Paulus, I. Grundke-Iqbal, P. Riederer, and M. B. H. Youdim, “Brain iron and ferritin in Parkinson's and Alzheimer's diseases,” Journal of Neural Transmission—Parkinson's Disease and Dementia Section, vol. 2, no. 4, pp. 327–340, 1990. View at Publisher · View at Google Scholar · View at Scopus
  114. H. Seznec, D. Simon, C. Bouton et al., “Friedreich ataxia: the oxidative stress paradox,” Human Molecular Genetics, vol. 14, no. 4, pp. 463–474, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. E. J. Kasarskis, L. Tandon, M. A. Lovell, and W. D. Ehmann, “Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study,” Journal of the Neurological Sciences, vol. 130, no. 2, pp. 203–208, 1995. View at Publisher · View at Google Scholar · View at Scopus
  116. K. D. Muirden and G. B. Senator, “Iron in the synovial membrane in rheumatoid arthritis and other joint diseases.,” Annals of the Rheumatic Diseases, vol. 27, no. 1, pp. 38–48, 1968. View at Publisher · View at Google Scholar · View at Scopus
  117. M.-K. Lim, C.-K. Lee, Y. S. Ju et al., “Serum ferritin as a serologic marker of activity in systemic lupus erythematosus,” Rheumatology International, vol. 20, no. 3, pp. 89–93, 2001. View at Publisher · View at Google Scholar · View at Scopus
  118. A. M. K. Choi and J. Alam, “Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury,” The American Journal of Respiratory Cell and Molecular Biology, vol. 15, no. 1, pp. 9–19, 1996. View at Publisher · View at Google Scholar · View at Scopus
  119. D. N. Seril, J. Liao, G. Y. Yang, and C. S. Yang, “Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models,” Carcinogenesis, vol. 24, no. 3, pp. 353–362, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Cai, K. C. Nelson, M. Wu, J. Sternberg P., and D. P. Jones, “Oxidative damage and protection of the RPE,” Progress in Retinal and Eye Research, vol. 19, no. 2, pp. 205–221, 2000. View at Publisher · View at Google Scholar · View at Scopus
  121. A. Wojas-Pelc and J. Marcinkiewicz, “What is a role of haeme oxygenase-1 in psoriasis? Current concepts of pathogenesis,” International Journal of Experimental Pathology, vol. 88, no. 2, pp. 95–102, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. K. J. Davies, A. Sevanian, S. F. Muakkassah-Kelly, and P. Hochstein, “Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid,” Biochemical Journal, vol. 235, no. 3, pp. 747–754, 1986. View at Google Scholar · View at Scopus
  123. A. Mutti, M. Corradi, M. Goldoni, M. V. Vettori, A. Bernard, and P. Apostoli, “Exhaled metallic elements and serum pneumoproteins in asymptomatic smokers and patients with COPD or asthma,” Chest, vol. 129, no. 5, pp. 1288–1297, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. L. W. Scheibel and A. Adler, “Antimalarial activity of selected aromatic chelators,” Molecular Pharmacology, vol. 18, no. 2, pp. 320–325, 1980. View at Google Scholar · View at Scopus
  125. E. D. Weinberg, “The hazards of iron loading,” Metallomics, vol. 2, no. 11, pp. 732–740, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. C. M. Witmer, “Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC),” Pediatric Clinics of North America, vol. 60, no. 6, pp. 1337–1348, 2013. View at Publisher · View at Google Scholar · View at Scopus
  127. S. Sazawal, R. E. Black, M. Ramsan et al., “Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial,” The Lancet, vol. 367, no. 9505, pp. 133–143, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. I. Kochan, “The role of iron in bacterial infections, with special consideration of host-tubercle bacillus interaction.,” Current Topics in Microbiology and Immunology, vol. 60, pp. 1–30, 1973. View at Google Scholar · View at Scopus
  129. M. J. Murray, A. B. Murray, M. B. Murray, and C. J. Murray, “The adverse effect of iron repletion on the course of certain infections,” British Medical Journal, vol. 2, no. 6145, pp. 1113–1115, 1978. View at Publisher · View at Google Scholar · View at Scopus
  130. I. T. Gangaidzo, V. M. Moyo, E. Mvundura et al., “Association of pulmonary tuberculosis with increased dietary iron,” Journal of Infectious Diseases, vol. 184, no. 7, pp. 936–939, 2001. View at Publisher · View at Google Scholar · View at Scopus
  131. J. L. Sullivan, “Iron and the sex difference in heart disease risk,” The Lancet, vol. 1, no. 8233, pp. 1293–1294, 1981. View at Google Scholar · View at Scopus
  132. X.-M. Yuan and W. Li, “The iron hypothesis of atherosclerosis and its clinical impact,” Annals of Medicine, vol. 35, no. 8, pp. 578–591, 2003. View at Publisher · View at Google Scholar · View at Scopus
  133. J. L. Sullivan, “Iron in arterial plaque: a modifiable risk factor for atherosclerosis,” Biochimica et Biophysica Acta, vol. 1790, no. 7, pp. 718–723, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. J. L. Sullivan, “Is stored iron safe?” Journal of Laboratory and Clinical Medicine, vol. 144, no. 6, pp. 280–284, 2004. View at Publisher · View at Google Scholar · View at Scopus