Skip to main content
SpringerLink
Log in

Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

To evaluate, in a longitudinal study, the profile of lipid peroxidation and antioxidant capacity markers in sickle cell anaemia patients receiving different treatments and medication over different time periods. The three groups were: patients undergoing transfusion therapy and receiving iron chelator deferasirox (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU group, n = 10), and patients receiving only folic acid (FA group, n = 15). Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent antioxidant capacity (TEAC) assays were evaluated during two different periods of analysis, T0 and T1 (after ~388 days). Higher FA group TBARS values were observed compared with the DFX + HU group (p = 0.016) at T0; and at T1, higher FA group TBARS values were also observed compared with both the DFX group (p = 0.003) and the DFX + HU group (p = 0.0002). No variation in TEAC values was seen between groups, at either T0 or T1. The mean values of TBARS and TEAC for both the DFX and DFX + HU groups decreased at T1. The antioxidant effects of HU and DFX were observed by through an increase in TEAC levels in DFX and DFX + HU groups when compared with those of normal subjects. Increased TEAC values were not recorded in the FA group, and lipid peroxidation was seen to decrease after DFX and HU use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Weatherall D, Hofman K, Rodgers G, Ruffin J, Hrynkow S (2005) A case for developing north–south partnerships for research in sickle cell disease. Blood 105:921–923

    Article  PubMed  CAS  Google Scholar 

  2. Bunn HF (1997) Mechanisms of disease—pathogenesis and treatment of sickle cell disease. N Engl J Med 337:762–769

    Article  PubMed  CAS  Google Scholar 

  3. Steinberg MH (1999) Management of sickle cell disease. N Engl J Med 340:1021–1030

    Article  PubMed  CAS  Google Scholar 

  4. Vekilov PG (2007) Sickle-cell haemoglobin polymerization: is it the primary pathogenic event of sickle-cell anaemia? Br J Haematol 139:173–184

    Article  PubMed  CAS  Google Scholar 

  5. Repka T, Hebbel RP (1991) Hydroxyl radical formation by sickle erythrocyte-membranes—role of pathological iron deposits and cytoplasmic reducing agents. Blood 78:2753–2758

    PubMed  CAS  Google Scholar 

  6. Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO III, Schechter AN et al (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 8:1383–1389

    Article  PubMed  CAS  Google Scholar 

  7. Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT (2009) Vasculopathy in sickle cell disease: biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol 84:618–625

    Article  PubMed  CAS  Google Scholar 

  8. Wood KC, Hebbel RP, Granger DN (2005) Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 19:989–991

    PubMed  CAS  Google Scholar 

  9. Belcher JD, Mahaseth H, Welch TE, Vilback AE, Sonbol KM, Kalambur VS et al (2005) Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice. Am J Physiol Heart Circ Physiol 288:H2715–H2725

    Article  PubMed  CAS  Google Scholar 

  10. Belcher JD, Bryant CJ, Nguyen J, Bowlin PR, Kielbik MC, Bischof JC et al (2003) Transgenic sickle mice have vascular inflammation. Blood 101:3953–3959

    Article  PubMed  CAS  Google Scholar 

  11. Frenette PS (2002) Sickle cell vaso-occlusion: multistep and multicellular paradigm. Curr Opin Hematol 9:101–106

    Article  PubMed  Google Scholar 

  12. Conran N, Franco-Penteado CF, Costa FF (2009) Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin 33:1–16

    Article  PubMed  CAS  Google Scholar 

  13. Rees DC, Williams TN, Gladwin MT (2010) Sickle-cell disease. Lancet 376:2018–2031

    Article  PubMed  CAS  Google Scholar 

  14. Covas DT, de Lucena Angulo I, Vianna Bonini PP, Zago MA (2004) Effects of hydroxyurea on the membrane of erythrocytes and platelets in sickle cell anemia. Haematologica 89:273–280

    PubMed  CAS  Google Scholar 

  15. Kinney TR, Helms RW, O’Branski EE, Ohene-Frempong K, Wang W, Daeschner C et al (1999) Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood 94:1550–1554

    PubMed  CAS  Google Scholar 

  16. Schnog JB, Duits AJ, Muskiet FA, ten Cate H, Rojer RA, Brandjes DP (2004) Sickle cell disease; a general overview. Neth J Med 62:364–374

    PubMed  CAS  Google Scholar 

  17. Halsey C, Roberts IAG (2003) The role of hydroxyurea in sickle cell disease. Br J Haematol 120:177–186

    Article  PubMed  CAS  Google Scholar 

  18. Hillery CA, Du MC, Wang WC, Scott JP (2000) Hydroxyurea therapy decreases the in vitro adhesion of sickle erythrocytes to thrombospondin and laminin. Br J Haematol 109:322–327

    Article  PubMed  CAS  Google Scholar 

  19. Lou TF, Singh M, Mackie A, Li W, Pace BS (2009) Hydroxyurea generates nitric oxide in human erythroid cells: mechanisms for gamma-globin gene activation. Exp Biol Med 234:1374–1382

    Article  CAS  Google Scholar 

  20. Adams RJ, Mckie VC, Hsu L, Files B, Vichinsky E, Pegelow C et al (1998) Prevention of a first stroke by transfusions in children with sickle, cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 339:5–11

    Article  PubMed  CAS  Google Scholar 

  21. Vichinsky E, Butensky E, Fung E, Hudes M, Theil E, Ferrell L et al (2005) Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia. Am J Hematol 80:70–74

    Article  PubMed  Google Scholar 

  22. Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M et al (2010) Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica 95:557–566

    Article  PubMed  CAS  Google Scholar 

  23. Steinberg MH (2008) Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. Scientific World Journal 8:1295–1324

    Article  PubMed  Google Scholar 

  24. Bonini-Domingos CR (2006) Metodologias laboratoriais para o diagnóstico de hemoglobinopatias e talassemias. NH, São José do Rio Preto

    Google Scholar 

  25. Belini E, Cancado RD, Domingos CRB (2010) The Xmnl polymorphic site 5′ to the gene G gamma in a Brazilian patient with sickle cell anaemia—fetal haemoglobin concentration, haematology and clinical features. Arch Med Sci 6:822–825

    Article  Google Scholar 

  26. Sutton M, Bouhassira EE, Nagel RL (1989) Polymerase chain-reaction amplification applied to the determination of beta-like globin gene-cluster haplotypes. Am J Hematol 32:66–69

    Article  PubMed  CAS  Google Scholar 

  27. Ondei LS, Silveira LM, Leite AA, Souza DR, Pinhel MA, Percario S et al (2009) Lipid peroxidation and antioxidant capacity of G6PD-deficient patients with A-(202G>A) mutation. Genet Mol Res 8:1345–1351

    Article  PubMed  CAS  Google Scholar 

  28. Uchiyama M, Mihara M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278

    Article  PubMed  CAS  Google Scholar 

  29. Miller NJ, Riceevans C, Davies MJ, Gopinathan V, Milner A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 84:407–412

    PubMed  CAS  Google Scholar 

  30. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237

    Article  PubMed  CAS  Google Scholar 

  31. Manfredini V, Lazzaretti LL, Griebeler IH, Santin AP, Brandao VDM, Wagner S et al (2008) Blood antioxidant parameters in sickle cell anemia patients in steady state. J Natl Med Assoc 100:897–902

    PubMed  Google Scholar 

  32. Jain SK, Ross JD, Levy GJ, Duett J (1990) The effect of malonyldialdehyde on viscosity of normal and sickle red blood cells. Biochem Med Metab Biol 44:37–41

    Article  PubMed  CAS  Google Scholar 

  33. Sertac A, Bingol F, Aydin S, Uslu A (1997) Peroxidative damage in sickle-cell erythrocyte ghosts: protective effect of allopurinol. Gen Pharmacol 28:427–428

    Article  PubMed  CAS  Google Scholar 

  34. Walter PB, Fung EB, Killilea DW, Jiang Q, Hudes M, Madden J et al (2006) Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol 135:254–263

    Article  PubMed  CAS  Google Scholar 

  35. Wood KC, Granger DN (2007) Sickle cell disease: role of reactive oxygen and nitrogen metabolites. Clin Exp Pharmacol Physiol 34:926–932

    Article  PubMed  CAS  Google Scholar 

  36. Aslan M, Ryan TM, Adler B, Townes TM, Parks DA, Thompson JA et al (2001) Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 98:15215–15220

    Article  PubMed  CAS  Google Scholar 

  37. Hebbel RP, Eaton JW, Balasingam M, Steinberg MH (1982) Spontaneous oxygen radical generation by sickle erythrocytes. J Clin Invest 70:1253–1259

    Article  PubMed  CAS  Google Scholar 

  38. Landburg PP, Teerlink T, Biemond BJ, Brandjes DP, Muskiet FA, Duits AJ et al (2010) Plasma asymmetric dimethylarginine concentrations in sickle cell disease are related to the hemolytic phenotype. Blood Cells Mol Dis 44:229–232

    Article  PubMed  CAS  Google Scholar 

  39. Xia Y, Dawson VL, Dawson TM, Snyder SH, Zweier JL (1996) Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc Natl Acad Sci USA 93:6770–6774

    Article  PubMed  CAS  Google Scholar 

  40. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V et al (2005) Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 294:81–90

    Article  PubMed  CAS  Google Scholar 

  41. Amer J, Ghoti H, Rachmilewitz E, Koren A, Levin C, Fibach E (2006) Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol 132:108–113

    Article  PubMed  CAS  Google Scholar 

  42. Schacter L, Warth JA, Gordon EM, Prasad A, Klein BL (1988) Altered amount and activity of superoxide dismutase in sickle cell anemia. FASEB J 2:237–243

    PubMed  CAS  Google Scholar 

  43. Hebbel RP, Osarogiagbon R, Kaul D (2004) The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation 11:129–151

    Article  PubMed  CAS  Google Scholar 

  44. Cighetti G, Duca L, Bortone L, Sala S, Nava I, Fiorelli G et al (2002) Oxidative status and malondialdehyde in beta-thalassaemia patients. Eur J Clin Invest 32:55–60

    Article  PubMed  CAS  Google Scholar 

  45. Hebbel RP, Morgan WT, Eaton JW, Hedlund BE (1988) Accelerated autoxidation and heme loss due to instability of sickle hemoglobin. Proc Natl Acad Sci USA 85:237–241

    Article  PubMed  CAS  Google Scholar 

  46. Scott MD (2006) H2O2 injury in beta thalassemic erythrocytes: protective role of catalase and the prooxidant effects of GSH. Free Radic Biol Med 40:1264–1272

    Article  PubMed  CAS  Google Scholar 

  47. Cao GH, Prior RL (1998) Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 44:1309–1315

    PubMed  CAS  Google Scholar 

  48. Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285

    Article  PubMed  CAS  Google Scholar 

  49. Fasola F, Adedapo K, Anetor J, Kuti M (2007) Total antioxidants status and some hematological values in sickle cell disease patients in steady state. J Natl Med Assoc 99:891–894

    PubMed  Google Scholar 

  50. Shimauti EL, Silva DG, de Almeida EA, Zamaro PJ, Belini Junior E, Bonini-Domingos CR (2010) Serum melatonin level and oxidative stress in sickle cell anemia. Blood Cells Mol Dis 45:297–301

    Article  PubMed  CAS  Google Scholar 

  51. Silva DG, Belini Junior E, Torres LS, Ricci Junior O, Lobo CC, Bonini-Domingos CR et al (2011) Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia. Blood Cells Mol Dis 47:23–28

    Article  PubMed  CAS  Google Scholar 

  52. Poillon WN, Kim BC, Rodgers GP, Noguchi CT, Schechter AN (1993) Sparing effect of hemoglobin-F and hemoglobin-A2 on the polymerization of hemoglobin-S at physiological ligand saturations. Proc Natl Acad Sci U S A 90:5039–5043

    Article  PubMed  CAS  Google Scholar 

  53. Dasgupta T, Fabry ME, Kaul DK (2010) Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. Am J Physiol Regul Integr Comp Physiol 298:R394–R402

    Article  PubMed  CAS  Google Scholar 

  54. Steinberg MH (2009) Genetic etiologies for phenotypic diversity in sickle cell anemia. Scientific World Journal 9:46–67

    Article  PubMed  Google Scholar 

  55. Agil A, Sadrzadeh SMH (2000) Hydroxy-urea protects erythrocytes against oxidative damage. Redox Rep 5:29–34

    PubMed  CAS  Google Scholar 

  56. Glickstein H, Ben El R, Link G, Breuer W, Konijn AM, Hershko C et al (2006) Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 108:3195–3203

    Article  PubMed  CAS  Google Scholar 

  57. Wood JC, Tyszka JM, Carson S, Nelson MD, Coates TD (2004) Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease. Blood 103:1934–1936

    Article  PubMed  CAS  Google Scholar 

  58. Kaul DK, Liu XD, Choong S, Belcher JD, Vercellotti GM, Hebbel RP (2004) Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice. Am J Physiol Heart Circ Physiol 287:H293–H301

    Article  PubMed  CAS  Google Scholar 

  59. Sultana C, Shen YM, Rattan V, Johnson C, Kalra VK (1998) Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes. Blood 92:3924–3935

    PubMed  CAS  Google Scholar 

  60. Vichinsky EP, Ohene-Frempong K (2011) Approaches to transfusion therapy and iron overload in patients with sickle cell disease: results of an international survey. Pediatr Hematol Oncol 28:37–42

    Article  PubMed  Google Scholar 

  61. Olivieri NF (1999) The beta-thalassemias. N Engl J Med 341:99–109

    Article  PubMed  CAS  Google Scholar 

  62. Porter JB (2001) Practical management of iron overload. Br J Haematol 115:239–252

    Article  PubMed  CAS  Google Scholar 

  63. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    PubMed  CAS  Google Scholar 

  64. Kolb AM, Smit NPM, Lentz-Ljuboje R, Osanto S, van Pelt J (2009) Non-transferrin bound iron measurement is influenced by chelator concentration. Anal Biochem 385:13–19

    Article  PubMed  CAS  Google Scholar 

  65. Koren A, Fink D, Admoni O, Tennenbaum-Rakover Y, Levin C (2010) Non-transferrin bound labile plasma iron and iron overload in sickle cell disease: a comparative study between sickle cell disease and beta thalassemic patients. Eur J Haematol 84:72–78

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the following Brazilian foundations: The National Council on Scientific Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); grant 409691/2006-2) and the Ministry of Health (grant MS 3072/2007) for their financial support.

Author information

Authors and Affiliations

  1. Department of Biology, Haemoglobin and Haematologic Diseases Genetic Laboratory, UNESP-Sao Paulo State University, Sao Jose do Rio Preto, Sao Paulo, Brazil

    Edis Belini Junior, Danilo Grünig Humberto da Silva, Lidiane de Souza Torres & Claudia Regina Bonini-Domingos

  2. Department of Haematology/Oncology, Santa Casa Medical School, Sao Paulo, Brazil

    Rodolfo Delfini Cancado & Carlos Chiattone

  3. Department of Chemistry and Environmental Sciences, UNESP-Sao Paulo State University, Sao Jose do Rio Preto, Sao Paulo, Brazil

    Danilo Grünig Humberto da Silva & Eduardo Alves de Almeida

  4. Department of Biology, Haemoglobin and Haematologic Diseases Genetic Laboratory, UNESP-Sao Paulo State University “Julio de Mesquita Filho”-IBILCE, Rua Cristovao Colombo, 2265-Jardim Nazareth, CEP 15054-000, Sao Jose do Rio Preto, Sao Paulo, Brazil

    Edis Belini Junior

Authors
  1. Edis Belini Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danilo Grünig Humberto da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lidiane de Souza Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eduardo Alves de Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rodolfo Delfini Cancado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlos Chiattone
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Claudia Regina Bonini-Domingos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edis Belini Junior.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belini Junior, E., da Silva, D.G.H., de Souza Torres, L. et al. Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time. Ann Hematol 91, 479–489 (2012). https://doi.org/10.1007/s00277-011-1340-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-011-1340-y

Keywords

Search

Navigation