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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities and subcellular distribution of enzymes implicated in the protection of cells from free-radical mediated damage were determined in liver biopsy specimens from control and iron-overloaded patients. 2. There was a small but insignificant decrease in the activity of glutathione reductase in patients with secondary iron overload due to multiple transfusion therapy for thalassaemia major. 3. The activities of superoxide dismutase, catalase and glutathione peroxidase were similar in both patient groups. 4. Subcellular fractionation studies indicated a major cytosolic localization of these enzymes with a minor mitochondrial component. The relative proportions of the enzymes in the two locations was similar in both control and iron-overloaded patients. 5. Approximately 80% of the hepatic glutathione was present in the reduced form in both patient groups and it is concluded that although free-radical mediated damage might be implicated in the pathogenesis of tissue damage due to iron overload no significant defect in these protective mechanisms can be demonstrated.
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PMID:Activities of some free-radical scavenging enzymes and glutathione concentrations in human and rat liver and their relationship to the pathogenesis of tissue damage in iron overload. 736 62

The 'antioxidant' enzymes superoxide dismutase (SD), catalase and glutathione peroxidase (GSH-Px) were found greatly elevated in red blood cells of subjects with beta-thalassaemia minor and similar to normal values in red blood cells of subjects with beta-thalassaemia major. These findings allows us to speculate that red cells in beta-thalassaemia minor react to the increased oxidant threat with augmented antioxidant enzyme activities. The normal levels of antioxidant enzymes in beta-thalassaemia major seem to be due to the presence of normal red cells owing to multiple transfusions.
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PMID:Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities in beta-thalassaemia (major and minor). 744 78

Haematological data, genotype, transfusion requirements, metabolic indicators of oxidative stress (flux via hexose-monophosphate shunt (HMPS); steady state level of GSH and GSSG, NADPH and NADP; activity of anti-oxidant enzymes), parameters of membrane damage (aggregated band 3; membrane-bound haemichromes, autologous immunoglobulins (Igs) and C3 complement fragments) and erythrophagocytosis were measured in erythrocytes (RBC) of 15 beta-thalassaemia intermedia patients (nine splenectomized) with low, if any, transfusion requirements. Patients presented increased aggregated band 3, bound haemichromes, Igs and C3 complement fragments, and increased erythrophagocytosis. Bound haemichromes strongly correlated with aggregated band 3. Anti-band 3 Igs were predominantly associated with aggregated band 3. Erythrophagocytosis positively correlated with aggregated band 3, haemichromes and Igs, suggesting the involvement of haemichrome-induced band 3 aggregation in phagocytic removal of beta-thalassaemic RBC. Splenectomized patients showed higher degrees of membrane damage and phagocytosis, significantly higher numbers of circulating RBC precursors, and tendentially higher numbers of reticulocytes. Basal flux via HMPS was increased twofold, but HMPS stimulation by methylene blue was decreased, as was the glucose flux via HMPS. GSH was remarkably decreased, whereas NADPH was increased. Except for unchanged catalase and glutathione reductase, anti-oxidant enzymes had increased activity. Negative correlation between HMPS stimulation by methylene blue and bound haemichromes indicated that the ability to enhance HMPS may counteract haemichrome precipitation and limit consequent membrane damage leading to erythrophagocytosis.
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PMID:Metabolic indicators of oxidative stress correlate with haemichrome attachment to membrane, band 3 aggregation and erythrophagocytosis in beta-thalassaemia intermedia. 1008 87

Neutrophils (PMNs) from patients with secondary iron overload have an increased iron and ferritin content as well as a phagocytosis defect. Several serum components might be incriminated in the cellular iron accumulation. We therefore compared the effects on the PMN phagocytosis of total serum as well as the ferritin and transferrin fractions of serum derived from patients with thalassemia major and healthy control subjects. An incubation system of PMNs was developed. PMN phagocytosis was measured before and after incubation. Total serum from patients with thalassemia induced a defect that was prevented by co-incubation with deferoxamine (DFO). Gel-filtration chromatography was performed to separate the serum fraction containing transferrin and albumin from that containing ferritin. The transferrin-albumin fraction had no effect on PMN phagocytosis. On the contrary, the ferritin fraction of normal serum was deleterious to PMN phagocytosis, and the same fraction from thalassemic serum decreased PMN phagocytosis even more. Co-incubation with DFO or catalase improved this defect. Moreover, a cellular increase in the L-type subunit of ferritin was observed after the incubation of PMNs with the ferritin-containing fraction from thalassemic serum. In conclusion, serum from patients with thalassemia is toxic to PMNs, and this toxicity is due to ferritin-associated iron.
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PMID:Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis. 1021 66

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.
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PMID:Interaction of antioxidants and their implication in genetic anemia. 1060 86

Anemia in beta-thalassemia is caused by a combination of ineffective erythropoiesis and premature hemolysis of RBC in the peripheral circulation. Excess of the alpha-globin chain present in beta-thalassemic RBC is mainly responsible for oxidative damage of erythrocyte membrane protein. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase, and the catalytic activity of catalase and superoxide dismutase, and the concentrations of non-enzymic antioxidants such as reduced glutathione were measured to estimate the status of the antioxidant defense system in the erythrocytes for protection against oxidative stress. The extent of lipid peroxidation was also estimated in thalassemic erythrocytes. Significantly lower activities of reduced glutathione indicate the cell to be in a pro-oxidant state and decreased activity of catalase favors hydrogen peroxide-mediated lipid peroxidation in beta-thalassemic and Ebeta-thalassemic RBC.
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PMID:Antioxidant defense status of red blood cells of patients with beta-thalassemia and Ebeta-thalassemia. 1124 31

Reactive oxygen species (ROS) contribute to the pathogenesis of several hereditary disorders of red blood cells (RBCs), including thalassaemia. We report here on a modified flow cytometric method for measuring ROS in normal and thalassaemic RBCs. RBCs were incubated with 0.4 mM 2',7'-dichlorofluorescin diacetate (DCFH-DA), then washed and further incubated either with or without 2 mM H2O2. Flow cytometric analysis showed that RBC fluorescence increased with time; it increased faster and reached higher intensity (by 10-30-fold) in H2O2-stimulated RBCs as compared to unstimulated RBCs. In both cases, the antioxidant N-acetyl-l-cysteine reduced fluorescence, confirming previous reports that DCFH fluorescence is mediated by ROS. While the fluorescence of unstimulated RBCs increased with time, probably because of exposure to atmospheric oxygen, in H2O2-stimulated RBCs fluorescence decreased after 30 min. The latter effect is most likely related to H2O2 decomposition by catalase as both sodium azide, an antimetabolite that inhibits catalase and low temperature increased the fluorescence of stimulated RBCs. Washing had a similar effect, suggesting that maintenance of the oxidised DCF requires a constant supply of ROS. We next studied RBCs of beta-thalassaemic patients. The results demonstrated a significantly higher ROS generation by stimulated and unstimulated thalassaemic RBCs compared to their normal counterparts. These results suggest that flow cytometry can be useful for measuring the ROS status of RBCs in various diseases and for studying chemical agents as antioxidants.
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PMID:Flow cytometric measurement of reactive oxygen species production by normal and thalassaemic red blood cells. 1258 Nov 89

The oxidative stress status of the transfusion-dependent Ebeta- and beta-thalassemia patients were studied before and after treatment with vitamin E for a period of four weeks. The level of cellular vitamin antioxidants viz. ascorbic acid and vitamin E in the thalassemia patients were found to be considerably lower compared to normal subjects. The activities of enzymatic antioxidants viz. catalase, glutathione peroxidase and glutathione reductase were found to be drastically reduced in untreated Ebeta- and beta-thalassemic patients when compared to normal subjects. However, the activity of superoxide dis-mutase was found to be increased in both types of untreated thalassemic patients when compared to normal individuals. An increase in superoxide dismutase and a decrease in catalase activity reflects the presence of a severe oxidative stress situation in the erythrocytes of the untreated transfusion dependent Ebeta- and beta-thalassemia patients. Changes in erythrocyte membrane protein pattern in untreated Ebeta- and beta-thalassemia patients when compared to normal erythrocyte further confirm the presence of continued oxidative stress in the ailing thalassemic erythrocytes. All these changes in the antioxidant status as well as the changes in the erythrocyte membrane proteins are ameliorated to considerable extent when the transfusion-dependent Ebeta- and beta-thalassemia patients were treated with vitamin E at a dose of 10 mg/kg/day for a period of four weeks. The patients during the treatment period did not exhibit any side effects and gained in body weight indicating a healthy status. The present study reveals that the lipophilic antioxidant vitamin E could be useful in the management of transfusion-dependant Ebeta- and beta-thalassemia patients.
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PMID:Attenuation of oxidative stress-induced changes in thalassemic erythrocytes by vitamin E. 1504 82

alpha-Thalassaemia is a common red cell disorder in Taiwan, affecting 6-8% of Taiwanese. Previous studies have shown that reactive oxygen species are generated in increased amounts in thalassaemic red cells. This implies the possible alteration of redox status in thalassaemic patients, which may adversely affect their health. In the present study, the redox status of patients with alpha-thalassaemia trait and haemoglobin H (Hb H) disease was investigated. Lipid peroxidation, as measured by the level of plasma thiobarbituric acid reactive substances (TBARS), was increased in alpha-thalassaemic patients, with the highest level of TBARS in Hb H disease patient. The plasma levels of vitamin A, C, and E were significantly lower in alpha-thalassaemic patients than in controls. The overall antioxidant capacity in plasma was inversely correlated with the severity of alpha-globin gene defect: the more severe the form of alpha-thalassaemia, the lower the overall antioxidant capacity in plasma. Erythrocytes isolated from alpha-thalassaemia patients had lower levels of vitamin E, glutathione, catalase and superoxide dismutase. In addition, these alpha-thalassaemic red cells were more susceptible to hydrogen peroxide-induced lipid peroxidation and decrease in deformability. All these data suggest that the alpha-thalassaemic patients suffer from increased oxidative stress and antioxidant deficit, which may complicate the pathophysiology of alpha-thalassaemia.
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PMID:Antioxidant deficit and enhanced susceptibility to oxidative damage in individuals with different forms of alpha-thalassaemia. 1560 58

Thalassemia is a group of genetic disorders resulting from different mutations in the globin gene complex and leading to an imbalance in globin synthesis. Unmatched globin chains are less stable and susceptible to oxidation. Patients with beta-thalassemia/HbE are prone to increased oxidative stress as indicated by increased lipid peroxidation product, malondialdehyde (MDA), partly because of the presence of iron in the form of heme and hemichromes released from excess globin chains and excess iron deposition in various tissues. The level of antioxidant such as glutathione is markedly decreased while activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) are increased. We have recently found that the levels of coenzyme Q(10) (CoQ(10)) are also very low in thalassemia. We therefore evaluated the oxidative stress and the antioxidants in these patients before and after supplementation with 100 mg CoQ(10) daily for 6 months. The results showed that the plasma level of CoQ(10) significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ(10) led to significant improvement of biochemical parameters of antioxidant enzymes. The antioxidant supplementation will be beneficial for thalassemia patients as adjunct therapy to increase their quality of life.
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PMID:Effect of coenzyme Q10 as an antioxidant in beta-thalassemia/Hb E patients. 1687 51


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