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Rev. Bras. Hematol. Hemoter. vol.33 número3

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Rev Bras Hematol Hemoter. 2011;33(3):172-8 177 xxx

Oxidative status in sickle cell anemia

Hematology Service, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brazil

Silvia Maria Meira Magalhães

Submitted: 7/4/2011 Accepted: 7/5/2011

Corresponding author:

Silvia Maria Meira Magalhães Serviço de Hematologia do Hospital Universitário Walter Cantídio Universidade Federal do Ceará Rua Capitão Francisco Pedro, 1290 – Rodolfo Teófilo

60430-370 – Fortaleza, CE, Brazil Phone: 55 85 3366-8623 silviamm@ufc.br

www.rbhh.org or www.scielo.br/rbhh

DOI: 10.5581/1516-8484.20110049

HbS polymerization is a primary pathophysiological event in sickle cell anemia (SCA). Hydroxyurea (HU) is one important therapy that offers broad benefits to a select group of patients with severe symptoms. HU induces higher levels of HbF thereby inhibiting the polymerization of HbS, acts on red blood cell hydration, vascular wall adherence and suppresses granulocyte and reticulocyte counts.

It has been suggested that oxidative stress plays a key role in many pathophysiological disorders and thus has gained increasing attention. Imbalance between production and elimination of reactive oxygen species (ROS) can damage cell structures, including lipids, membranes, proteins and nucleic acids resulting in cell death or altered cell function. However, the role of free radicals is not fully known and most evidence is indirect; consensual reference ranges and interpretation are lacking.

Although results are sometimes contradictory, patients with SCA are shown to have high oxidative stress. Sickle cells spontaneously generate approximately two times more ROS compared to normal red blood cells; this is associated with endothelial dysfunction,

inflammation and multiple organ damage and is related to the severity of clinical features.(1,2)

In addition, multiple transfusions cause accumulation of pathological non-transferrin-bound iron that catalyzes the generation of ROS.

(2)

178 Rev Bras Hematol Hemoter. 2011;33(3):172-8

reproducibility, costs and clinical meaning, however recognized shortcomings of different methods must be taken into account.

Amounts of antioxidants are interesting parameters in themselves. The measurements of reduced glutathione (GSH) and its oxidized form glutathione disulfide (GSSG) have been considered useful indicators of the status of oxidative stress. A decrease in the GSH concentration and its antioxidant capacity has been associated with the pathogenesis of SCA. In the paper by Teixeira Neto PF et al., GSH levels were shown to be significantly higher in HU treated patients when compared to untreated patients

suggesting a therapy-related antioxidant effect.(3)

HU was shown to significantly reduce lipid

peroxidation levels in treated patients.(4) Some recent

studies have shown that the HbF protective effect is primarily mediated by decreased intravascular sickling, resulting in reduced oxidative stress and also in increased

nitric oxide bioavailability.(5) HU treatment may therefore

be correlated to lower oxidative status and better antioxidative defense.

However, the use of an isolated biomarker to evaluate oxidative stress and measurement of individual antioxidants are not likely to be useful indexes of oxidative status. The

oxidant-antioxidant balance involves biochemical reactions that require the evaluation of many endpoints.

The true relationship between oxidative status with HU treatment remains unclear and warrants further studies.

References

1. Rusanova I, Escames G, Cossio G, Borace RG, Moreno B, Chahboune M, et al. Oxidative stress status, clinical outcome and -globin gene cluster haplotypes in pediatric patients with sickle cell disease. Eur J Haematol. 2010; 85(6):529-37. Doi: 10.1111/j.1600-0609.2010.01528.x.

2. Hundekar P, Suryakar A, Karnik A, Ghone R, Vasaikar M. Antioxidant status and lipid peroxidation in sickle cell anaemia. Biomedical Research. 2010;21(4):461-4.

3. Teixeira Neto PF, Gonçalves RP, Elias DBD, Araújo CP, Magalhães HIF. Analysis of oxidative status and biochemical parameters in adult patients with sickle cell anemia treated with hydroxyurea, Ceará-Brazil. Rev Bras Hematol Hemoter. 2011;33(3):207-10. 4. Silva DG, Belini Junior E, Torres LS, Ricci Junior O, Lobo CC,

Bonini-Domingos CR, et al. Blood Cells Mol Dis. 2011;47(1):23-8. Epub 2011 Apr 12.

5. Dasgupta T, Fabry ME, Kaul DK. 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. 2010;298(2):R394-402. Epub 2009 Dec 9.

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