Abstract
Iron deficiency is frequently associated with anemia. Iron is a transition-metal ion, and it can induce free radical formation, which leads to formation of various lesions in DNA, proteins, and lipids. The aim of this study was to investigate baseline oxidative DNA damage and to clarify the role of the administration of a therapeutic dose of iron on DNA oxidation in children with iron deficiency anemia (IDA). Twenty-seven children with IDA and 20 healthy children were enrolled in the study. Leukocyte DNA damage (strand breaks and Fpg-sensitive sites) was assessed using comet assay before and after 12 weeks of daily iron administration. Before the iron administration, the frequency of DNA strand breaks in the children with IDA was found to be lower than those in the control group (P < 0.05), but there was not a significant difference for frequency of Fpg-sensitive sites. After 12 weeks of iron administration, the frequency of both DNA strand breaks and Fpg-sensitive sites were found to be increased (P < 0.01). No significant association was determined between DNA damage parameters and hemoglobin, hematocrit, serum iron, total iron binding capacity, and ferritin. In conclusion, basal level of DNA strand breaks is at a low level in children with IDA. After iron administration, DNA strand breaks and Fpg-sensitive sites, which represent oxidatively damaged DNA, increased. However, this increase was unrelated to serum level of iron and ferritin.
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References
Acharya J, Punchard NA, Taylor JA, Thompson RP, Pearson TC (1991) Red cell lipid peroxidation and antioxidant enzymes in iron deficiency. Eur J Haematol 47:287–291
Aslan M, Horoz M, Kocyigit A, Ozgonul S, Celik H, Celik M, Erel O (2006) Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutation Res 601(1–2):144–149
Bacon BR, Britton SR (1990) The pathology of hepatic iron overload: a free radical mediated process. Hepatology 11(1):127–134
Bartal M, Mazor D, Dvilansky A, Meyerstein N (1993) Iron deficiency anemia: recovery from in vitro oxidative stres. Acta Haematol 90:94–98
Berrak SG, Angaji M, Turkkan E, Canpolat C, Timur C, Eksioglu-Demiralp E (2007) The effects of iron deficiency on neutrophil/monocyte apoptosis in children. Cell Prolif 40(5):741–754
Binet JL, Mentz F, Merle-Beral H (1996) Apoptosis in blood diseases. Review new data. Hematol Cell Ther 38(3):253–264
Cachofeiro V, Goicochea M, de Vinuesa SG, Oubina P, Lahera V, Luno J (2008) Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl (111):S4–S9
Candiano G, Petretto A, Bruschi M, Santucci L, Dimuccio V, Prunotto M, Gusmano R, Urbani A, Ghiggeri GM (2009) The oxido-redox potential of albumin methodological approach and relevance to human diseases. J proteomics 73(2):188–195
Collins AR, Ai-guo M, Duthie SJ (1995) The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutat Res 336:69–77
Collins AR, Dobson VL, Dusinska M, Kennedy G, Stetina R (1997) The comet assay: what can it really tell us? Mutat Res 375:183–193
Collins AR, Raslova K, Somorovska M, Petrovska H, Ondrusova A, Vohnout B, Fabry R, Dusinska M (1998) DNA damage in diabetes: correlation with a clinical marker. Free Radic Biol Med 25(3):373–377
Dincer Y, Akcay T, Alademir Z, Ilkova H (2002) Assesment of DNA base oxidation and glutathione level in patients with type 2 diabetes. Mutat Res 505(1–2):75–81
Dizdaroglu M (1991) Chemical determination of free radical-induced damage to DNA. Free Radic Biol Med 10:225–242
Evans MD, Dizdaroglu M, Cooke MS (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567(1):1–61
Galleano M, Puntarulo S (1995) Role of antioxidant on the erythrocyte resistance to lipid peroxidation after acut iron overload in rats. Biochim Biophys Acta 1271(3):321–326
Glader B (2004) Iron-deficiency anemia. In: Behrmann RE, Kliegman RM, Jenson HB (eds) Nelson textbook of pediatrics, 17th edn. WB Saunders, Philadelphia, pp 1614–1616
Green MHL, Love JE, Delaney CA, Green IC (1996) Comet assay to detect nitric oxide-dependent DNA damage in mammalian cells. Methods Enzymol 269:243–266
Jansson LT, Perkkio MV, Willis WT, Refino CJ, Dalman PR (1985) Red cell superoxide dismutase is increased in iron deficiency anemia. Acta Haematol 74:218–221
Kumerova A, Lece A, Skesters A, Silova A, Petuhovs V (1998) Anaemia and antioxidant defence of the red blood cells. Mater Med Pol 30(1–2):12–15
Lindeman JH, Lentjes EG, van Zoeren-Grobben D, Berger HM (2000) Postnatal changes in plasma ceruloplasmin and transferrin antioxidant activities in preterm babies. Biol Neonate 78(2):73–76
Mimic-Oka J, Savic-Radojevic A, Pljesa-Ercegovac M, Opacic M, Smic T, Dimkovic N, Simic DV (2005) Evaluation of oxidative stress after repeated intravenous iron supplementation. Ren Fail 27(3):345–351
Miranda A, Janssen L, Bosman CB, Van Duijin NW, Ostendorp-Van de Ruit MM, Kubben FJGM, Griffioen G, Lamers CBHW, Han J, Van Krieken JM, Van de Velde CJH, Verspaget HW (2000) Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer. Clin Cancer Res 6(8):3183–3192
Ramachandran M, Iyer GY (1984) Erythrocyte membrane lipid peroxidation in iron deficiency anemia. Experientia 40:173–174
Reed JC (1997) Cytochrome c: can't live with it—can't live without it. Cell 91(5):559–562
Rice-Evans CY, Baysal E (1987) İron-mediated oxidative stres in erythrocytes. Biochem J 244:191–196
Rockey DC, Cello JP (1993) Evaluation of the gastrointestinal tract in patients with iron deficiency anemia. N Engl J Med 329:1691–1695
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Steele RJ, Thompson AM, Hall PA, Pane DP (1998) The p53 tumour suppressor gene. Br J Surg 85(11):1460–1467
Stockman JA (1993) Anemia of iron deficiency. In: Burg FD, Ingelfinger JR, Wald ER (eds) Current pediatric therapy, 14th edn. WB Saunders, Philadelphia, pp 238–240
Sun Y (1990) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 8:583–589
Vaux DL, Strasser A (1996) The molecular biology of apoptosis. Proc Natl Acad Sci USA 93:2239–2244
Vives Corrons JL, Miguel-Garcia A, Pujades MA, Miguel-Sosa A, Cambiazzo S, Linares M, Dibarrart MT, Calvo MA (1995) Increased susceptibility of microcytic red blood cells to in vitro oxidative stress. Eur J Haematol 55(5):327–331
Zaidi A, Marden MC, Poyart C, Leclerc L (1995) Protection by Lazoroids of erythrocyte (Ca2+, Mg2+)-ATPase against iron induced inhibition. Eur J Pharmacol 290(2):133–139
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Aksu, B.Y., Hasbal, C., Himmetoglu, S. et al. Leukocyte DNA damage in children with iron deficiency anemia: effect of iron supplementation. Eur J Pediatr 169, 951–956 (2010). https://doi.org/10.1007/s00431-010-1147-1
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DOI: https://doi.org/10.1007/s00431-010-1147-1
Keywords
- Iron deficiency anemia
- DNA strand breaks
- Fpg-sensitive sites
- Comet assay
- Iron supplementation