Comparison of Hematological and Biochemical Parameters which Indicate Inflammatory and Oxidative Status Between Pediatric Patients with Iron Deficiency but Without Anemia and Age-matched Healthy Subjects

Abstract

Objectives: We aimed to investigate the relationship between iron deficiency without anemia and thiol disulphide homeostasis, which effected oxidative status. Materials and Methods: A total of 71 cases, including the 5-15 age group with iron deficiency (n=35) and age- and gender-matched healthy control group (n=36), who applied to the pediatric outpatient clinic, were enrolled in the study. The diagnosis of iron deficiency was established for the patients who had normal hemoglobin levels considering age and gender, and whose ferritin value was <12 ng/mL. Results: Ferritin levels were 11.01±0.89 ng/mL in patients with iron deficiency and 25.27±2.57 ng/mL in healthy controls (p<0.001). In patients with iron deficiency, native thiol and total thiol levels were significantly lower (p<0.001 and p<0.001, respectively), and disulphide, disulphide/native thiol ratio and disulphide/total thiol ratio were significantly higher (p<0.001, p<0.001 and p<0.001, respectively). Only total thiol levels had positive correlation with ferritin levels (r=0.330, p=0.049). Conclusion: In this study, we showed that iron deficiency has effect on oxidative stress.

Keywords

• Iron Deficiency
• Oxidative Stress
• Thiol Disulphide Homeostasis

Demir Eksikliği Tespit Edilip Anemi Tespit Edilmeyen Hastalar ile Yaş Uyumlu Sağlıklı Kontroller Arasındaki Enflamasyon ve Oksidatif Durumu Gösteren Hematolojik ve Biyokimyasal Parametrelerin Karşılaştırılması

Abstract

Amaç: Anemi olmadan demir eksikliği olan hastalar ile oksidatif durumu etkileyen tiyol disülfid dengesi arasındaki ilişkinin ortaya konulması amaçlanmıştır. Gereç ve Yöntem: Pediatri polikliniğinde başvuran 5-15 yaş aralığı demir eksikliği (n=35) olan grup ile yaş ve cinsiyet uyumlu sağlıklı kontrol grubunun (n=36) oluşturduğu toplam 71 olgu çalışmaya dahil edildi. Demir eksikliği tanısı, yaş ve cinsiyete göre normal hemoglobin seviyesine sahip olup, ferritin değeri <12 ng/mL altında olan hastalara konuldu. Bulgular: Demir eksikliği grubunda ferritin düzeyi 11,01±0,89 ng/mL iken, kontrol grubunda ise 25,27±2,57 ng/mL idi (p<0,001). Demir eksikliği grubunda nativ tiyol ve total tiyol değerleri anlamlı olarak düşükken (p<0,001 ve p<0,001, sırasıyla), disülfid, disülfid/nativ tiyol ve disülfid/total tiyol değerleri anlamlı olarak yüksekti (p<0,001, p<0,001 ve p<0,001, sırasıyla). Ferritin düzeyi ile sadece total tiyol düzeyi arasında pozitif korelasyon mevcuttu (r=0,330, p=0,049). Sonuç: Bu çalışmada anemi olmadan da demir eksikliğinin oksidatif strese neden olduğu izlendi.

Keywords

• Demir Eksikliği
• Oksidatif Stres
• Tiyol Disülfid Dengesi

References

1. 1. Andrews NC KR. Disorders of iron metabolism ve sideroblastik anemia. Philadelphia: WB Saunders; 1998.
2. 2. Andrews NC UC, Fleming MD. Disorders of Iron Metabolism and Sideroblastic Anemia. 7 ed. Philadelphia: W.B. Saunders Company.; 2009.
3. 3. Dallman PR, Yip R, Johnson C. Prevalence and causes of anemia in the United States, 1976 to 1980. Am J Clin Nutr. 1984;39:437-445.
4. 4. Khusun H, Yip R, Schultink W, et al. World Health Organization hemoglobin cut-off points for the detection of anemia are valid for an Indonesian population. J Nutr. 1999;129:1669-1674.
5. 5. Nancy C AK. Disorders of iron metabolism and sideroblastik anemia. Philadelphia: W.B Saunders; 1998.
6. 6. Berçem İ, İçağasıoğlu D, Cevit Ö, et al. Sivas’ta 12-18 yaş grubu adolesanlarda demir eksikliği anemisi prevalansı. Türkiye Klinikleri Pediatri Dergisi. 1999;8:15-20.
7. 7. B G. Iron-deficiency anemia. 17 ed. Philadelphia: W.B Saunders; 2004.
8. 8. Aslan M, Horoz M, Kocyigit A, et al. Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutat Res. 2006;601:144-149. 9. Nagababu E, Chrest FJ, Rifkind JM. Hydrogen-peroxide-induced heme degradation in red blood cells: the protective roles of catalase and glutathione peroxidase. Biochim Biophys Acta. 2003;1620:211-217.

9. 10. Hori A, Mizoue T, Kasai H, et al. Body iron store as a predictor of oxidative DNA damage in healthy men and women. Cancer Sci. 2010;101:517-522.
10. 11. Cremers CM, Jakob U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem. 2013;288:26489-26496.
11. 12. Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009;47:1329-1338.
12. 13. Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010;15:8890-8903.
13. 14. Go YM, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol Med. 2011;50:495-509.
14. 15. Prabhu A, Sarcar B, Kahali S, et al. Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res. 2014;74:787- 796.
15. 16. Tetik S, Ahmad S, Alturfan AA, et al. Determination of oxidant stress in plasma of rheumatoid arthritis and primary osteoarthritis patients. Indian J Biochem Biophys. 2010;47:353-358.
16. 17. Rodrigues SD, Batista GB, Ingberman M, et al. Plasma cysteine/cystine reduction potential correlates with plasma creatinine levels in chronic kidney disease. Blood Purif. 2012;34:231-237.
17. 18. Sbrana E, Paladini A, Bramanti E, et al. Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patients. Electrophoresis. 2004;25:1522-1529.
18. 19. Calabrese V, Lodi R, Tonon C, et al. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J Neurol Sci. 2005;233:145-162.
19. 20. Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med. 2013;62:13-25.
20. 21. Steele ML, Fuller S, Maczurek AE, et al. Chronic inflammation alters production and release of glutathione and related thiols in human U373 astroglial cells. Cell Mol Neurobiol. 2013;33:19-30.
21. 22. Kuo LM, Kuo CY, Lin CY, et al. Intracellular glutathione depletion by oridonin leads to apoptosis in hepatic stellate cells. Molecules. 2014;19:3327-3344.
22. 23. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47:326-332.
23. 24. Oski FA BC, Nathan DG. A diagnostic approach to anemic patient. Philadelphia: Saunders; 1998.
24. 25. B Ç. Çocuklarda demir eksikliği anemisi tedavisinde kullanılan farklı demir preparatlarının plazmada oksidan stres ve eritrositlerde antioksidan sistem üzerine olan etkilerinin araştırılması. İzmir 2002.
25. 26. Choi JW, Pai SH, Kim SK, et al. Iron deficiency anemia increases nitric oxide production in healthy adolescents. Ann Hematol. 2002;81:1-6.
26. 27. Drysdale JW, Adelman TG, Arosio P, et al. Human isoferritins in normal and disease states. Semin Hematol. 1977;14:71-88.
27. 28. Seymen O, Seven A, Candan G, et al. The effect of iron supplementation on GSH levels, GSH-Px, and SOD activities of erythrocytes in L-thyroxine administration. Acta Med Okayama. 1997;51:129-133.
28. 29. Slivka A, Kang J, Cohen G. Hydroxyl radicals and the toxicity of oral iron. Biochem Pharmacol. 1986;35:553-556.
29. 30. Acharya J, Punchard NA, Taylor JA, et al. Red cell lipid peroxidation and antioxidant enzymes in iron deficiency. Eur J Haematol. 1991;47:287-291.
30. 31. Isler M, Delibas N, Guclu M, et al. Superoxide dismutase and glutathione peroxidase in erythrocytes of patients with iron deficiency anemia: effects of different treatment modalities. Croat Med J. 2002;43:16-19.
31. 32. Jansson LT, Perkkiö MV, Willis WT, et al. Red cell superoxide dismutase is increased in iron deficiency anemia. Acta Haematol. 1985;74:218-221.
32. 33. Kumerova A, Lece A, Skesters A, et al. Anaemia and antioxidant defence of the red blood cells. Mater Med Pol. 1998;30:12-15.
33. 34. Panchenko LF, Lamchingiĭn T, Gerasimov AM, et al. Aktivnost’ superoksiddismutazy krovi deteĭ s zhelezodefitsitnymi anemiiami [Superoxide dismutase activity in the blood of children with iron deficiency anemia]. Vopr Med Khim. 1979;25:181-185.
34. 35. Cellerino R, Guidi G, Perona G. Plasma iron and erythrocytic glutathione peroxidase activity. A possible mechanism for oxidative haemolysis in iron deficiency anemia. Scand J Haematol. 1976;17:111-116.
35. 36. Tekin D, Yavuzer S, Tekin M, et al. Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia. Pediatr Int. 2001;43:74-77.
36. 37. McAnulty LS, Gropper SS, McAnulty SR, et al. Iron depletion without anemia is not associated with impaired selenium status in college-aged women. Biol Trace Elem Res. 2003;91:125-136.
37. 38. Gropper SS, Kerr S, Barksdale JM. Non-anemic iron deficiency, oral iron supplementation, and oxidative damage in college-aged females. J Nutr Biochem. 2003;14:409-415.
38. 39. Hamed HM, Motawie AA, Abd Al-Aziz AM, et al. Low Dose Iron Therapy in Children with Iron Deficiency: DNA Damage and Oxidant Stress Markers. Indian journal of hematology & blood transfusion: an official journal of Indian Society of Hematology and Blood Transfusion. 2021;37:287-94.
39. 40. Bektas H, Vural G, Gumusyayla S, et al. Dynamic thiol-disulfide homeostasis in acute ischemic stroke patients. Acta Neurol Belg. 2016;116:489-494.
40. 41. Ates I, Kaplan M, Yuksel M, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine. 2016;51:47-51.
41. 42. Topal I, Mertoglu C, Sürücü Kara I, et al. Thiol-Disulfide Homeostasis, Serum Ferroxidase Activity, and Serum Ischemia Modified Albumin Levels in Childhood Iron Deficiency Anemia. Fetal Pediatr Pathol. 2019;38:484-489.