ABSTRACT
This study was aimed at investigating oxidative stress in thalassemic patients by measurement of the oxidative damage biomarker, F(2)-isoprostanes (F(2)-IsoPs), using gas chromatography-mass spectrometry. The results showed that the mean value of urinary F(2)-IsoPs, normalized with creatinine, in the thalassemic group was significantly higher than that from healthy subjects (3.38+/-2.15 ng/mg creatinine vs 0.86+/-0.55 ng/mg creatinine, respectively), and the mean value of plasma total F(2)-IsoPs in the thalassemic group was also significantly higher than that from healthy subjects (0.39+/-0.15 ng/ml vs 0.18+/-0.03 ng/ml, respectively). Serum ferritin, erythrocyte superoxide dismutase (SOD), glutathione peroxidase, glutathione, and TBARS levels after treatment of erythrocytes with H(2)O(2) were also investigated, and serum ferritin and erythrocyte SOD levels were significantly higher in thalassemic patients. Our findings are consistent with oxidative stress in thalassemia patients.
Subject(s)
F2-Isoprostanes/metabolism , Thalassemia/metabolism , Adult , Antioxidants/metabolism , Bilirubin/blood , Biomarkers/metabolism , Case-Control Studies , Erythrocyte Indices , Erythrocytes/metabolism , F2-Isoprostanes/blood , F2-Isoprostanes/urine , Female , Ferritins/blood , Humans , Male , Middle Aged , Oxidative Stress , Thalassemia/blood , Thalassemia/urine , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Oxidative stress in thalassemia is caused by secondary iron overload and stems from blood transfusion and increased iron uptake. In this study, we hypothesized that levels of o- and m-tyrosine, products of hydroxyl radical attack on phenylalanine, would be elevated in beta-thalassemia (intermediate). This study represents the first report in which specific markers of protein oxidative damage have been quantified in thalassemia. We used GC/MS to assay o- and m-tyrosine at the femtomole level using only a few microliters of plasma. Levels of both markers were significantly higher in patients with beta-thalassemia than in controls and were positively correlated with serum ferritin, malondialdehyde, superoxide dismutase, glutathione peroxidase and glutathione. We conclude that o- and m-tyrosine are useful biomarkers of oxidative damage to proteins in thalassemia (intermediate) and may also be useful markers in other iron overload diseases. Positive correlations between o- and m-tyrosine levels and malondialdehyde as well as antioxidants such as superoxide dismutase, glutathione peroxidase and glutathione, are indicative of the broad impact of oxidative stress on blood plasma in thalassemia, with up-regulation of antioxidant proteins probably reflecting a homeostatic response to these increased stress levels.
