Search

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 β-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 β-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. [ABSTRACT FROM AUTHOR]

Abstract: Thalassemic diseases including homozygous β-thalassemia and β-thalassemia/Hb E (β-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in β-thalassemia patients which induces intracellular oxidative stress and lipid peroxidation (LPO). LPO end products generate miscoding etheno adducts in DNA which after their repair are excreted in urine. We investigated whether urinary levels of 1,N 6 -ethenodeoxyadenosine (εdA) and 3,N 4 -ethenodeoxycytidine (εdC) can serve as putative cancer risk markers in β-Thal/Hb E patients. εdA and εdC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P-postlabeling TLC, respectively. Mean εdA (fmol/µmol creatinine) levels in urine of β-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8±3.9; n =37) and were 8.7 times higher compared to asymptomatic controls (1.4–13.8; 3.9±0.8; n =20). The respective εdC levels ranged from 0.15 to 32.5 (5.2±1.3; n =37) and were increased some 13 times over controls (0.04–1.2; 0.4±0.7; n =20). εdC levels were correlated positively with NTBI (r =0.517; P =0.002), whereas εdA showed only a trend (r =0.257; P =0.124). We conclude that the strongly increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA damage in internal organs such as the liver. These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma. [Copyright &y& Elsevier]

Abstract: This study was aimed at investigating oxidative stress in thalassemic patients by measurement of the oxidative damage biomarker, F2-isoprostanes (F2-IsoPs), using gas chromatography-mass spectrometry. The results showed that the mean value of urinary F2-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 F2-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 H2O2 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. [Copyright &y& Elsevier]

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.

Nine patients with either beta-thalassaemia/haemoglobin E (7) or homozygous beta-thalassaemia (2) not requiring regular transfusions were treated with the oral iron chelator, deferiprone 25-50 mg/kg/d for between 17 and 86 weeks (mean 49 weeks). There were significant decreases in serum ferritin (initial mean +/- standard deviation 2168 +/- 1142, final 418 +/- 247 micro g/l; t-test for paired samples, P = 0.005), hepatic iron (initial 20.3 +/- 6.26, final 11.7 +/- 4.83 mg/g/dry weight; P = < 0.02), red cell membrane iron (initial 76.2 +/- 3.64, final 7.2 +/- 0.56 mmol/mg protein; P = < 0.0005) and serum non-transferrin bound iron (initial 9.0 +/- 0.56, final 5.9 +/- 0.89 micro mol/l; P = < 0.0005). There was also a significant rise in serum erythropoietin (initial 240 +/- 195.1, final 433.2 +/- 269.2 U/l; P = 0.034). The haemoglobin level rose in three patients and transfusion requirements were reduced substantially in four patients. Serum thiobarbituric acid reactive substance (TBARS) also fell in six of eight patients. Patients generally improved clinically, with weight gain observed. Side-effects were mild and included gastrointestinal symptoms (6) and arthralgia (1), not requiring withdrawal of the drug. One patient died at 17 weeks of therapy as a result of an intercurrent infection. His neutrophil count was normal. We conclude that deferiprone is an effective, well-tolerated iron chelator for patients with thalassaemia intermedia. Further studies are needed to determine the optimum dose and length of treatment needed to reduce iron burden to a safe level in these patients.