Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythrocyte catalase, reduced glutathione, glutathione peroxidase and glutathione reductase were determined in 17 normal black controls, 8 subjects with Hb AC, 12 with Hb SC, 1 with Hb CC and 18 patients with sickle cell anemia. Catalase and glutathione peroxidase activities were decreased in sickle cell anemia. Reduced glutathione and glutathione reductase activity were significantly lower in subjects with Hb C (AC, CC, SC). Differences were observed between Hb C, Hb S and Hb A as regards red cell dehydration, intracellular crystallization, enhanced potassium efflux, an increased number of titratable SH groups in Hb C and the binding of Hb C to band 3 on the inner membrane surface. A decrease in reduced glutathione, probably due to inhibition or decreased synthesis of glutathione reductase, was also observed. All these factors may determine oxidation of Hb C, possibly contributing to the hemolysis in patients with Hb C disease.
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PMID:Decreased reduced glutathione and glutathione reductase activity in subjects with hemoglobin C. 194 19

Levels of plasma selenium (Se) and glutathione peroxidase were measured in 20 sickle cell anemia (SCA) patients not in crisis and in 14 nonanemic control subjects. The results show that the levels of Se and glutathione peroxidase were significantly (p less than 0.005) lower than those of controls in both plasma and whole blood. These data are consistent with the previous reports that there is increased oxidative stress in SCA. Low blood Se levels and glutathione peroxidase activity observed in this research suggest that a weakened antioxidant potential may be associated with SCA patients. The low Se status in SCA patients may also affect the phenotypic expression of these patients.
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PMID:Selenium and glutathione peroxidase levels in sickle cell anemia. 158 63

Erythrocytes containing abnormal haemoglobins with high affinity for red cell membrane are subjected to enhanced oxidant stress. Since HbS is known to have high affinity for red cell membrane and sickle cells are particularly susceptible to membrane lipid peroxidation, the behaviour of erythrocyte antioxidant system has been evaluated in 20 subjects, heterozygous for sickle cell anaemia. These subjects have shown normal levels of reduced glutathione, increased superoxide dismutase and glutathione peroxidase activities and low catalase activity. These data suggest that such an unbalanced antioxidant system can not prevent damage by the enhanced production of oxygen free radicals by membrane-bound HbS molecules.
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PMID:Antioxidant system in sickle red cells. 641 Jun 46

Whole blood glutathione peroxidase was found significantly increased relative to controls in a group of 21 black patients with sickle cell anaemia. One control group consisted of 15 normal black subjects. A second control group, consisting of 21 black patients with various abnormal haemoglobins including alpha-thalassaemia, also showed a tendency to enhanced glutathione peroxidase activity, confirming previous reports that elevated glutathione peroxidase levels are secondary to a variety of haemolytic conditions, rather than typical of sickle cell anaemia.
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PMID:Glutathione peroxidase activity in whole blood of patients with sickle cell anaemia. 723 85

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

Bacillus polyfermenticus SCD, commonly referred to as Bispan strain, is used as a host in bioindustry and has been shown to have several human health benefits. In a recent in vitro study, we discovered that B. polyfermenticus SCD exerts cholesterol-lowering and antioxidant effects. Here, we evaluate the effects of B. polyfermenticus SCD on the lipid and antioxidant metabolisms of hypercholesterolemic rats. Twenty male Sprague-Dawley rats were divided into two groups after a 1-week adaptation period and were fed for 6 weeks on either a high fat-high cholesterol diet, or a high fat-high cholesterol diet supplemented with B. polyfermenticus SCD (3.1x10(6) cfu/d). B. polyfermenticus SCD significantly reduced plasma low-density-lipoprotein cholesterol, hepatic total cholesterol, and triglycerides, while increasing the fecal excretion rates of total cholesterol and triglycerides. In addition, B. polyfermenticus SCD might reduce the risk of atherosclerosis, as the ratio of high-density-lipoprotein cholesterol to total cholesterol was significantly higher than in the control group. B. polyfermenticus SCD led to an increase in total radical trapping antioxidant potential (TRAP) and a decrease in conjugated dienes in plasma. The erythrocytic glutathione peroxidase (GSH-Px) activity in the B. polyfermenticus group was significantly lower than that in the control group. Plasma TRAP levels exhibited a highly significant negative correlation with hepatic total cholesterol and a marginally significant negative correlation with total plasma cholesterol, while a significant positive correlation was detected between fecal total cholesterol and plasma TRAP. These results suggest that B. polyfermenticus SCD exerts significant health benefits through the modulation of physiologic functions including a variety of atherogenic lipid profiles and antioxidants in hypercholesterolemia.
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PMID:Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet. 1599 12

Sickle cell disease (SCD) is characterized by reperfusion injury and chronic oxidative stress. Oxidative stress and hemolysis in SCD result in inactivation of nitric oxide (NO) and depleted arginine levels. We hypothesized that augmenting NO production by arginine supplementation will reduce oxidative stress in SCD. To this end, we measured the effect of arginine (5% in mouse chow) on NO metabolites (NOx), lipid peroxidation (LPO), and selected antioxidants in transgenic sickle mouse models. Untreated transgenic sickle (NY1DD) mice (expressing approximately 75% beta(S)-globin of all beta-globins; mild pathology) and knockout sickle (BERK) mice (expressing exclusively hemoglobin S; severe pathology) showed reduced NOx levels and significant increases in the liver LPO compared with C57BL mice, with BERK mice showing maximal LPO increase in accordance with the disease severity. This was accompanied by reduced activity of antioxidants (glutathione, total superoxide dismutase, catalase, and glutathione peroxidase). However, GSH levels in BERK were higher than in NY1DD mice, indicating a protective response to greater oxidative stress. Importantly, dietary arginine significantly increased NOx levels, reduced LPO, and increased antioxidants in both sickle mouse models. In contrast, nitro-L-arginine methylester, a potent nonselective NOS inhibitor, worsened the oxidative stress in NY1DD mice. Thus, the attenuating effect of arginine on oxidative stress in SCD mice suggests its potential application in the management of this disease.
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PMID:Protective effect of arginine on oxidative stress in transgenic sickle mouse models. 1715 80

Sickle cell anemia (SCA) is a hereditary disorder with higher potential for oxidative damage due to chronic redox imbalance in red cells. We measured antioxidant enzymes including catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also determined oxidative damage of proteins in hemolysate of red blood cells (RBCs) and plasma (carbonyl assay). We characterized the membrane damage in terms of lipid peroxidation by accumulation of malonaldehyde (MDA) by HPLC in 30 healthy controls and 20 SCA patients in steady-state condition. Twenty (9 males/11 females) adult SCA patients and 30 healthy controls were studied. All patients and control subjects had antioxidant (CAT, GPx, SOD, carbonyl and MDA) and hematological parameters done. Our data show that SCA patients had significant higher GPx and SOD activities than healthy controls. Carbonyl assay was noted in plasma but not in hemolysate. An enhanced production of MDA was observed in the serum of SCA patients. Our data support the growing evidence that patients with SCA are subjected to chronic oxidative stress and are able to oxidative damage in biological macromolecules such as proteins and lipids.
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PMID:Blood antioxidant parameters in sickle cell anemia patients in steady state. 1871 39

In sickle cell disease (SCD), the events originating from hemoglobin S polymerization and intravascular sickling lead to reperfusion injury, hemolysis, decreased nitric oxide (NO) bioavailability, and oxidative stress. Oxidative stress is implicated as a contributing factor to multiple organ damage in SCD. We hypothesize that inhibition of sickling by genetic manipulation to enhance antisickling fetal hemoglobin (HbF) expression will have an ameliorating effect on oxidative stress by decreasing intravascular sickling and hemolysis and enhancing NO bioavailability. We tested this hypothesis in BERK (Berkeley) mice expressing exclusively human alpha- and beta(S)-globins and varying levels of HbF, i.e., BERK (<1% HbF), BERKgammaM (20% HbF) and BERKgammaH (40% HbF). Intravascular sickling showed a distinct decrease with increased expression of HbF, which was accompanied by decreased hemolysis and increased NO metabolites (NO(x)) levels. Consistent with decreased intravascular sickling and increased NO bioavailability, BERKgammaM and BERKgammaH mice showed markedly decreased lipid peroxidation accompanied by increased activity/levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and reduced glutathione (GSH)] in the muscle, kidney, and liver compared with BERK mice (P < 0.05-0.0001). NO(x) levels showed a strong inverse correlation with hemolytic rate and oxidative stress. Decreased oxidative stress in the presence of elevated HbF levels led to an anti-inflammatory effect as evidenced by decreased peripheral leukocyte counts. These results show that the protective effect of HbF is mediated primarily by decreasing intravascular sickling resulting in decreased oxidative stress and increased NO bioavailability.
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PMID:Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. 2000 16

Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A, C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p<0.00001), GSH(reduced) (p<0.00001) and GSSG (p>0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p<0.00001), while antioxidant defense expressed as FORD was significantly reduced (p<0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status.
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PMID:Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status. 2133 30


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