Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study to investigate the association between blood glutathione (GSH) levels and biliary excretory status was conducted in apparently healthy Ghanaian subjects without frank biliary disease and anaemia. The results showed that, in adults (mean age: 38.5 years) and children (mean age: 13.0 years), plasma conjugated bilirubin is inversely correlated with blood GS (respective site r = -0.524, p < 0.011 and -0.395, p < 0.005). Persons with elevated plasma conjugated bilirubin compared to controls (mean: 6.0 versus 2.5 umol/L, p < 0.001) also exhibited low blood GSH values (3.5 versus 4.2 umol/gHb, p < 0.029). Malaria parasites with counts up to 2,453 parasites/ul blood had no effect on the obtained data. The results suggest that low blood GSH levels may be relevant to delays in biliary excretion of conjugated toxins from the liver, as exemplified by the rise in conjugated bilirubin levels in the plasma, and predispose liver cells to increased oxidant state and damage.
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PMID:Biliary excretion in persons with low blood glutathione levels. 974 34

This study examined whether lead-induced alterations in selected parameters that are indicative of oxidative stress accompany the toxic effects of lead in red blood cells (RBCs) in vivo. It also explored the possibility that treatment with N-acetylcysteine (NAC) or succimer (meso-2,3-dimercaptosuccinic acid) was capable of reversing parameters indicative of lead-induced oxidative stress. Fisher 344 rats were given 2000 ppm lead acetate in their drinking water for 5 weeks. The lead was then removed and the animals were given NAC (800 mg/kg/day) or succimer (90 mg/kg/day) in their drinking water for 1 week, after which the RBCs were harvested. Animals not given lead and those given lead, but not NAC or succimer, served as negative and positive controls, respectively. At the end of the experiment, blood-lead levels were 35 +/- 4 microg/dl in lead-treated animals, which were reduced to 2.5 +/- 1 microg/dl by treatment with succimer and to 25 +/- 3 microg/dl by treatment with NAC. Lead-exposed animals demonstrated signs of anemia as evidenced by anisocytosis, poikilocytosis, and alterations in hemoglobin, hematocrit, and mean corpuscular volume. Lipid peroxidation, as evidenced by increased malondialdehyde (MDA) content, as well as decreases in reduced glutathione (GSH) and increases in catalase and glucose 6-phosphate dehydrogenase (G6PD) activity were noted in RBCs from lead-treated rats, suggesting that the lead induced oxidative stress. In addition, a significant reduction in blood delta-aminolevulinic acid dehydratase (ALAD) activity suggested that accumulation and autooxidation of delta-aminolevulinic acid might contribute to lead-induced oxidative stress. Treatment with either NAC or succimer reversed lead-induced alterations in MDA and GSH content, but only succimer appeared to partially restore ALAD activity. These results provide in vivo evidence supporting the hypothesis that lead induces oxidative stress in RBCs, which is reversible by treatment with a thiol antioxidant (NAC), as well as a chelating agent (succimer).
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PMID:Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats. 975 41

Antioxidant defence was investigated in red blood cells (RBC) in 56 patients with 3 different haemoblastoses: polycythemia vera (PV), chronic myelogenous leukaemia (CML), chronic lymphoid leukemia (CLL) with and without anaemia, in 12 iron deficiency anaemia (A) patients and 50 healthy persons. The activities were determined of the following antioxidant enzymes: glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and MDA levels. Antioxidant defence is decreased and the level of lipid peroxidation are increased in RBC in all patients (PV, CML, CLL, A). Different changes were detected in the antioxidative defence between normal red blood cells and those formed from leukaemic cells clone. In normal RBC in anaemia (CLL, A) opposite deviation of G6PD and GSSG-R activities was observed. In RBC formed from leukaemic cell clone (PV, CML), a simultaneous significant increase in G6PD and GSSG-R activities was found, which indicated activisation of pentose phosphate pathways (PPP) in these pathologies; in anaemia they function less effectively.
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PMID:Anaemia and antioxidant defence of the red blood cells. 1021 69

Nitrobenzene (NB) human cancer studies have not been reported, but animals studies have. Three rodent strains inhaling NB produce cancer at eight sites. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced in the cecum and systemically in the microsomes to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN). Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. Reduced NB first forms the nitroanion free radical, which can react with O2 to form superoxide O2*. Repeated NB dosing produces a persistent redox couple NOB<==>PH in red blood cells (RBCs) that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione (GSH) conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known NB effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. On the basis of animal, metabolic and structure-activity studies, NB is determined to be a probable human carcinogen by any route of exposure.
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PMID:Nitrobenzene carcinogenicity in animals and human hazard evaluation. 1048 55

To assess the extent of oxidative stress in erythrocytes of patients with acute Plasmodium falciparum malaria, erythrocyte thiobarbituric acid-reactive substance (ETBAR), and intracellular, membrane and extracellular antioxidants were estimated in 102 cases of P. falciparum malaria and 50 control subjects. The mean concentration of ETBAR was significantly higher (P < 0.001) and many of the antioxidants were significantly lower in patients than controls. Among the erythrocyte antioxidants, catalase, reduced glutathione (GSH) and tocopherol were significantly lower in the patients (P < 0.05, 0.001, 0.001, respectively). Erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were not reduced to a statistically significant level. Similarly, the plasma antioxidants ascorbate and albumin were significantly lower (P < 0.001) but not urate. ETBAR correlated inversely with erythrocyte GSH and tocopherol (P < 0.001), and plasma ascorbate and albumin (P < 0.001) but not with the erythrocyte enzymic antioxidants. However, on multiple regression analysis only tocopherol correlated strongly with ETBAR, followed by GSH and plasma ascorbate. ETBAR also correlated well with haemolytic indices such as haemoglobin, plasma unconjugated bilirubin and haptoglobin concentrations (P < 0.001, for all). On follow-up after 2 weeks, ETBAR and different antioxidants reached near control levels. These observations indicate an enhanced oxidative stress on erythrocytes in acute falciparum malaria that may contribute substantially to haemolysis and anaemia.
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PMID:Evidence for erythrocyte lipid peroxidation in acute falciparum malaria. 1049 92

Glutathione (GSH) is the primary antioxidant in humans. Oxidative cellular injury is postulated to be centrally involved in diverse processes including aging, cancer, cardiovascular disease, and Human Immunodeficiency Virus (HIV) disease progression. Normal plasma GSH concentrations have been well characterized in healthy children and adults, but not during infant development. The objectives of this study were to: a) measure plasma GSH concentrations in non-infected infants born from HIV-infected mothers, to b) assess the developmental variations with age and gender, and c) evaluate for possible associations with growth, anemia, and other maternal and infant variables. One hundred and seventy (170) plasma samples from 44 HIV-uninfected infants (birth to 18 mos.) born to HIV-infected mothers from the Women and Infant Transmission Study (Puerto Rico site) were analyzed. The total plasma GSH geometric mean concentration for all samples analyzed was 1.94 (1.06) mumoles/L. A developmental effect of age was seen with lower concentrations in younger infants (0-2 months) than in older infants 4-18 months. There was no significant effect of gender, anemia, zidovudine exposure, maternal age, maternal CD4 cell percent, or infant growth, although a trend towards increasing GSH concentration was seen with increasing weight for height z-score. These findings have multiple clinical ramifications including prediction of capacity to detoxify oxidants at different ages, and partial explanation for the increased viral loads seen in HIV-infected infants.
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PMID:Plasma glutathione concentrations in non-infected infants born from HIV-infected mothers: developmental profile. 1054 71

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

In addition to facilitating the nuclear export of incompletely spliced viral mRNAs, equine infectious anemia virus (EIAV) Rev regulates alternative splicing of the third exon of the tat/rev mRNA. In the presence of Rev, this exon of the bicistronic RNA is skipped in a fraction of the spliced mRNAs. In this report, the cis-acting requirements for exon 3 usage were correlated with sequences necessary for Rev binding and transport of incompletely spliced RNA. The presence of a purine-rich exon splicing enhancer (ESE) was required for exon 3 recognition, and the addition of Rev inhibited exon 3 splicing. Glutathione-S-transferase (GST)-Rev bound to probes containing the ESE, and mutation of GAA repeats to GCA within the ESE inhibited both exon 3 recognition in RNA splicing experiments and GST-Rev binding in vitro. These results suggest that Rev regulates alternative splicing by binding at or near the ESE to block SR protein-ESE interactions. A 57-nucleotide sequence containing the ESE was sufficient to mediate Rev-dependent nuclear export of incompletely spliced RNAs. Rev export activity was significantly inhibited by mutation of the ESE or by trans-complementation with SF2/ASF. These results indicate that the ESE functions as a Rev-responsive element and demonstrate that EIAV Rev mediates exon 3 exclusion through protein-RNA interactions required for efficient export of incompletely spliced viral RNAs.
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PMID:Binding of equine infectious anemia virus rev to an exon splicing enhancer mediates alternative splicing and nuclear export of viral mRNAs. 1077 44

Visceral leishmaniasis (V.L.) is associated with enhanced lipid peroxidation along with impaired function of antioxidant defense system in erythrocytes. The effect of chronic treatment with ascorbate and alpha-tocopherol was studied on erythrocytes in hamsters infected with Leishmania donovani. Combination treatment with both antioxidants proved to be a potential suppressor of lipid hydroperoxide formation as well as hypotonic osmotic lysis during the leishmanial infection. Positive correlations between the depleted levels of erythrocyte ascorbate, GSH and alpha-tocopherol exhibit proportionate alterations in the nonenzymatic antioxidant levels at different stages of infection. Indirect measurement of transmembrane electron transfer as ferricyanide reduction suggests an active participation of endogenous contents of ascorbate and alpha-tocopherol in the protection against oxidative damage of membrane lipids. Cooperative behavior of both antioxidants in the ferricyanide reducing capacity was further evinced by resealing the ghosts in presence of exogenous ascorbate and alpha-tocopherol. Furthermore, intravesicular ascorbate serves in the defense of extravesicular ferricyanide induced oxidation of endogenous alpha-tocopherol. The results suggest an interacting role of ascorbate and alpha-tocopherol in maintaining the antioxidant reserve of erythrocytes during anemia in V.L.
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PMID:Interaction of ascorbate and alpha-tocopherol enhances antioxidant reserve of erythrocytes during anemia in visceral leishmaniasis. 1119 25

A rare case of hereditary erythrocyte enzymopathy, namely 6-phosphogluconate dehydrogenase (6PGD) deficiency, was found in an Italian family. The activity of the enzyme was reduced to 35% in the propositus and her mother, but was normal in the other three members of the family. The 6PGD deficiency was associated with a variable reticulocyte count and recurrent increased unconjugated bilirubinemia without anemia in the propositus, while no clinical or hematological symptoms were evident in her mother. Increased levels of erythrocyte pyruvate kinase (PK) activity and reduced glutathione (GSH) were observed, indicating a slight decrease in mean red blood cell (RBC) age and an activation of reducing systems. The episodic hemolytic events with jaundice observed in the propositus may be the result of a defective RBC ability to counteract conditions of marked oxidative stress. In this report the importance of 6PGD estimation for a proper analysis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is also highlighted. In fact in the present study, the presence of 6PGD deficiency could be mistaken for a partial G6PD deficiency if the assay of G6PD activity was performed without correcting for 6PGD activity.
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PMID:6-Phosphogluconate dehydrogenase deficiency in an Italian family. 1123 75


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