Abnormal red blood cell morphological changes in thalassaemia associated with iron overload and oxidative stress.

Aims: Iron overload is a major factor contributing to the overall pathology of thalassaemia, which is primarily mediated by ineffective erythropoiesis and shorter mature red blood cell (RBC) survival. Iron accumulation in RBCs generates reactive oxygen species (ROS) that cause cellular damage such as lipid peroxidation and RBC membrane deformation. Abnormal RBCs in patients with thalassaemia are commonly known as microcytic hypochromic anaemia with poikilocytosis.

Elevated levels of miR-210 correlate with anemia in β-thalassemia/HbE patients.

Ineffective erythropoiesis in β-thalassemia patients is caused by the premature death of red blood cell precursors due to excess α-globin chains. As a consequence, patients develop chronic anemia and hypoxia. Upregulation of miR-210, a hypoxia-induced miRNA, has been shown to regulate globin gene expression and erythroid differentiation in β-thalassemia/HbE erythroid progenitor cell culture.

Discrimination of various thalassemia syndromes and iron deficiency and utilization of reticulocyte measurements in monitoring response to iron therapy.

Decreased hemoglobinization of red cells resulting in hypochromia and microcytosis are the main features of thalassemia syndromes, and also of iron deficiency anemia (IDA). A simple and reliable method is required to distinguish the two conditions in the routine laboratories. In this study we analyzed the red cell and reticulocyte parameters from 414 samples of various types of thalassemias and IDA and discovered a variety of discriminating criteria including a discrimination index (DI) which should be useful for differential diagnosis.

Cardiomyocyte ultrastructural damage in β-thalassaemic mice.

β-thalassaemia is a hereditary anaemia resulting from the absence or reduction in β-globin chain production. Heart complications related to iron overload are the most serious cause of death in these patients. In this report cardiac pathology of β-thalassaemic mice was evaluated by light and electron microscopy.

Accumulation of lipid peroxidation-derived DNA lesions in iron-overloaded thalassemic mouse livers: comparison with levels in the lymphocytes of thalassemia patients.

In thalassemia patients, iron overload can stimulate lipid peroxidation (LPO), thereby generating miscoding DNA adducts. Adducted DNA was measured in the lymphocytes of beta-Thal/Hb E patients and healthy controls and in the organs of thalassemic mice. epsilondA, epsilondC and M(1)dG residues were quantified by (32)P-postlabeling-TLC/HPLC.

Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia 1, or beta-thalassemia and in compound heterozygotes for HbE/beta-thalassemia.

Background: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons.

Objective: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes.

Design: In Thai women (n = 103), red blood cell indexes, iron status, non-transferrin-bound iron, and growth differentiation factor 15 were measured, and body iron was calculated.

Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: markers for lipid peroxidation-induced DNA damage.

Thalassemic diseases including homozygous beta-thalassemia and beta-thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in beta-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.

Elevated F2-isoprostanes in thalassemic patients.

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.

Quantitative determination of ortho- and meta-tyrosine as biomarkers of protein oxidative damage in beta-thalassemia.

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.

A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.

Background: Thalassemia may alter the pharmacokinetics of several drugs in thalassemic patients. Paracetamol is a commonly used analgesic and antipyretic drug which is extensively metabolized in the liver via glucuronidation. The aim of this study was to compare the pharmacokinetics of paracetamol (PCM) and its metabolites [paracetamol glucuronide (PCM-G), paracetamol sulfate (PCM-S), and paracetamol cysteine (PCM-C)] in 16 patients with 16 normal subjects.

Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator.

Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and beta-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.

Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand.

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.

Labile plasma iron in iron overload: redox activity and susceptibility to chelation.

Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for catalyzing the formation of reactive radicals in the circulation of iron overloaded subjects, resulting in accumulation of oxidation products. We assessed the redox active component of NTBI in the plasma of healthy and beta-thalassemic patients. The labile plasma iron (LPI) was determined with the fluorogenic dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted by ascorbate but blocked by iron chelators.

A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in thai patients with thalassemia.

The variety of patients with thalassemia in Thailand offers an opportunity to fully characterize the kinetic causes of the anemia and to study apoptosis of marrow erythroid precursors as a possible factor contributing to its severity. Kinetic studies showed that in hemoglobin H (HbH) disease, the extent of hemolysis, as well as the minimally ineffective erythropoiesis, usually falls within the compensatory capacity of normal erythropoiesis; therefore, anemia in patients with HbH partly represents a failure to expand erythropoiesis adequately. Hemoglobin Constant Spring (HbCS), a common variant of alpha thalassemia in Bangkok, causes more severe hemolysis and a distinct increase in ineffective erythropoiesis.