Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease - PubMed (original) (raw)

Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease

Patrick B Walter et al. Br J Haematol. 2006 Oct.

Abstract

Blood transfusion therapy is life-saving for patients with beta-thalassaemia and sickle cell disease (SCD), but often results in severe iron overload. This pilot study examined whether the biomarkers of tissue injury or inflammation differ in these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1.8-fold in thalassaemia relative to control patients. In contrast, MDA in SCD was not significantly different from controls. In multivariate analysis, the strongest predictors of elevated MDA were liver iron concentration (P < 0.001) and specific diagnosis (P = 0.019). A significant 2-fold elevation of non-transferrin bound iron (NTBI) was observed in thalassaemia relative to SCD. NTBI was not a significant predictor of high MDA in multivariate analysis. SCD patients showed a significant 2.2-fold elevation of the inflammatory marker interleukin (IL)-6 relative to controls, and a 3.6- and 1.7-fold increase in IL-5 and IL-10 relative to thalassaemia. Although alpha-tocopherol was significantly decreased by at least 32% in both thalassaemia and SCD, indicating ongoing oxidant stress and antioxidant consumption, gamma-tocopherol, a nitric oxide-selective antioxidant, was increased 36% in SCD relative to thalassaemia. These results demonstrate that thalassaemia patients have increased MDA and circulating NTBI relative to SCD patients and lower levels of some cytokines and gamma-tocopherol. This supports the hypothesis that the biology of SCD may show increased inflammation and increased levels of protective antioxidants compared with thalassaemia.

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Figures

Fig 1

Fig 1

Regression analysis comparing plasma malondialdehyde (MDA) (nmol/l, log scale) with liver iron concentration [mg/g dry weight (dw)]. Regressions for thalassaemia (top; R = 0.695, P = 0.003) and sickle cell disease (bottom; R = 0.644, P = 0.032), show that, in both diseases, higher liver iron concentrations are associated with more plasma MDA.

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References

    1. Aslan M, Freeman BA. Oxidant-mediated impairment of nitric oxide signaling in sickle cell disease – mechanisms and consequences. Cellular and Molecular Biology. 2004;50:95–105. - PubMed
    1. Aslan M, Thornley-Brown D, Freeman BA. Reactive species in sickle cell disease. Annals of the New York Academy of Sciences. 2000;899:375–391. - PubMed
    1. Aslan M, Ryan TM, Adler B, Townes TM, Parks DA, Thompson JA, Tousson A, Gladwin MT, Patel RP, Tarpey MM, Batinic-Haberle I, White CR, Freeman BA. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proceedings of the National Academy of Sciences of the Unites States of America. 2001;98:15215–15220. - PMC - PubMed
    1. Aslan M, Ryan TM, Townes TM, Coward L, Kirk MC, Barnes S, Alexander CB, Rosenfeld SS, Freeman BA. Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization. Journal of Biological Chemistry. 2003;278:4194–4204. - PubMed
    1. Banerjee T, Kuypers FA. Reactive oxygen species and phosphatidylserine externalization in murine sickle red cells. British Journal of Haematology. 2004;124:391–402. - PubMed

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