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)

Both anemia and zinc deficiency are commonly observed in patients with chronic uremia. Oxidative stress of red blood cells (RBC) has been suggested to participate in the development of anemia in these patients with chronic uremia due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of oxidative stress on RBC of chronic uremia is still not understood. We thus performed the study to determine the influence of zinc deficiency on the oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce chronic uremia. Experiment was carried out in the following five groups: normal control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx-D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic fragility and lipid peroxidation of RBC were used to evaluate the oxidative stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a syndrome of uremia to elevate the levels of plasma creatinine and urea, and reduce the level of plasma zinc (1.12 +/- 0.08 vs 1.35 +/- 0.05 ug/ml). But they does not find to produce anemia and to increase osmotic fragility and lipid peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX. Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in red cells did not increase, because of the increase of plasma copper level (1.85 +/- 0.3 vs 1.41 +/- 0.05 microg/ml) and RBC-SOD activity (1.95 +/- 0.27 vs 0.78 +/- 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the appetite and normalized the levels of plasma zinc, copper and selenium. Food restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and increased osmotic fragility of RBC and elevated the susceptibility of lipid peroxidation after stressing RBC with H2O2 Because Nx-PF rats presented a lower RBC-SOD activity (0.44 +/- 0.11 vs 0.78 +/- 0.05 unit/g Hb) and a lower plasma copper level. We further found a positive relationship (r=0. 802,p<0.01) between plasma copper level and RBC-SOD activity in normal and uremic rats. This study suggests that RBC-SOD activity may play an important role in preventing RBC oxidative stress. Plasma copper level may be a marker of RBC-SOD activity. We conclude, in chronic uremia, zinc deficiency doses not result in RBC oxidative stress as plasma copper level is normal, but may affect the absorption of intestinal nutrition.
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PMID:Absent effect of zinc deficiency on the oxidative stress of erythrocytes in chronic uremic rats. 1200 52

Dietary nutrient interactions are important factors to consider in the study of nutrient status and requirements. Here, the effects of dietary interactions among copper (Cu), iron (Fe), manganese (Mn) and sulfur amino acids (SAA) on blood cell characteristics and enzyme activities were observed. Male rats (n = 8) were used in a 2 x 2 x 2 x 2 factorial design and fed an AIN-93G-based diet containing dietary Cu (<1 and 5 mg/kg), Fe (10 and 35 mg/kg), Mn (10 and 50 mg/kg) and either L-cystine (LCys) or DL-methionine (DLMet). Blood was analyzed by automated hematology cell counting and by flow cytometry. Severe Cu deficiency was verified by reductions in the activities of serum ceruloplasmin (1% of control), RBC superoxide dismutase (SOD1) (14% of control), liver cytochrome c oxidase activity (25% of control) and serum extracellular SOD (SOD3) activity (20% of controls). Because Cu is required for Fe utilization, many physiologic responses that require Fe were affected by both deficiencies, including lowered blood hemoglobin (Hgb), lower RBC volume and Hgb concentration, and an increased number of reticulocytes. Cu and Fe deficiencies together worsened some conditions, i.e., lower Hgb, lower RBC Hgb, increased RBC distribution width, increased number of reticulocytes and nucleated RBC, and a higher platelet count. Increasing dietary Mn had little effect on most variables, except to reduce serum Cu when dietary Cu was adequate but not when it was low, and to reduce RBC SOD1 activity when dietary Fe was low but not when it was adequate. Hgb concentrations were higher (P < 0.002) in Cu-deficient rats fed LCys than in those fed DLMet. There was no effect in Cu-adequate rats. Hgb was higher (P < 0.004) in Fe-adequate rats fed LCys than in those fed DLMet, with no effect in Fe-deficient rats. Although the anemia of Cu deficiency in AIN-93G-fed rats was not as pronounced as that reported in rats fed the AIN-76A-based diet, other manifestations of the deficiency were prominent.
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PMID:Contrasting and cooperative effects of copper and iron deficiencies in male rats fed different concentrations of manganese and different sources of sulfur amino acids in an AIN-93G-based diet. 1474 82

An intensification of aminolevulinic acid (ALA)-synthase on the day of experiment and its tend to its further gradual inhibition noted to be in the bone marrow cells of rats with alimentary iron-deficient anemia (IDA). An activity of porfobilinogen (PB)-synthase was increasing in all the terms of the trial, that of ferrochelatase--on the day 10, and it was inhibited later on. Such changes in an activity of heme synthesis key enzymes result in an accumulation of intermittent products. An increase in MDA level, an inhibition of antioxidant defense enzymes found to be in all the terms of trial, SOD--in all the terms of studies, catalase--in late terms.
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PMID:[Activity of heme synthesis enzymes in the bone marrow cells of rats with alimentary iron-deficient anemia]. 1577 Oct 77

To assess the antioxidant status and oxidative stress in bovine theileriosis due to Theileria annulata blood samples were collected from 35 clinically affected cattle referred to Veterinary Teaching Hospital, School of Veterinary Medicine, Urmia University, Urmia, Iran. Complete blood count, piroplasm parasitemia percentage, erythrocyte glutathione peroxidase, superoxide dismutase, catalase and glucose-6-phosphate dehydrogenase activities, malondialdehyde concentration, osmotic fragility test and median corpuscular fragility were determined and the results were compared with those of 50 healthy controls. Of 35 affected cattle, 12 (34.28%) had severe anemia and 23 had mild to moderate anemia and parasitemia varied from 5 to 40%. The activities of erythrocyte glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase were significantly lower (P<0.0001) and the activity of catalase was significantly higher in the affected cattle than in healthy ones (P<0.001). Malondialdehyde concentration in erythrocytes of affected cattle was significantly more than those of healthy cattle (P<0.001). The affected cattle showed increased fragility of erythrocytes, so that median corpuscular fragility (MCF) in affected group was significantly lower than those of healthy group (P<0.0001). Median corpuscular fragility showed a positive correlation with the severity of parasitemia (r=0.81, P<0.0005) and a negative correlation with the activities of GSH-Px (r=-0.78, P<0.0001), SOD (r=-0.71, P<0.0005), catalase (r=-0.53, P<0.018) and G6PD (r=-0.58, P<0.0005). The results of this study suggest that oxidative damage to RBCs may contribute to the pathogenesis of anemia in bovine theileriosis.
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PMID:Evaluation of antioxidant status and oxidative stress in cattle naturally infected with Theileria annulata. 1690 49

Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, SOD1-/- mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1-/- mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD1 deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase II, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.
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PMID:Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production. 1705 87

Venous (maternal) and cord blood (neonatal) samples of Omani women who had a daily supplement of Centrum Materna multivitamin and multimineral tablet throughout pregnancy were investigated at late preterm (n=37) and at term (n=37) delivery for erythrocyte indices, micromineral, antioxidant, and lipid values. Hemoglobin (Hb), hematocrit (HCT), mean cell volume (MCV), red cell distribution width (RDW), copper (Cu), zinc (Zn), ceruloplasmin, erythrocyte Cu-Zn superoxide dismutase (Cu-Zn SOD), cholesterol, apolipoprotein (apo) A-I and apo B were measured by appropriate analytical systems. Cu/zinc and Cu/ceruloplasmin ratios were calculated. The erythrocyte indices were normal in neonatal blood but showed borderline anemia in maternal blood of both groups. There were significantly decreased values of Cu (P=0.012), Zn (P=0.001), apo A-I (P=0.029), and Cu/ceruloplasmin ratio (P=0.032) in late preterm compared to term mothers. Significantly decreased values of Cu (P=0.003), ceruloplasmin (P<0.0001), apo A-I (P=0.024), and Cu/Zn ratio (P=007) were observed in late preterm relative to term neonates. Late preterm mothers were significantly younger (P=0.027) than term mothers. Maternal age correlated positively with apo A-I (r=0.424, P=0.012) and negatively with Cu/Zn ratio (r=-0.353, P=0.040). The findings suggest that with daily dietary Centrum Materna supplementation throughout pregnancy, hematological indices were maintained within normal in mothers and neonates, but the levels of microminerals and micromineral ratios were subnormal in late preterm mothers and their neonates.
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PMID:Erythrocyte indices, microminerals and ratios, antioxidants and lipids in Centrum Materna diet-supplemented Omani mothers. 1841 56

The essentiality of copper (Cu) in humans is demonstrated by various clinical features associated with deficiency, such as anaemia, hypercholesterolaemia and bone malformations. Despite significant effort over several decades a sensitive and specific Cu status biomarker has yet to be identified. The present article updates a comprehensive review recently published by the authors which assesses the reliability and robustness of current biomarkers and outlines the on-going search for novel indicators of status(1). The essential features of this earlier review are reiterated whilst considering whether there are other approaches, not yet tested, which may provide valuable information in the quest for an appropriate measure of copper status. Current biomarkers include a range of cuproenzymes such as the acute phase protein caeruloplasmin and Cu-Zn-superoxide dismutase all of which are influenced by a range of other dietary and environmental factors. A recent development is the identification of the Cu chaperone, CCS as a potential biomarker; although its reliability has yet to be established. This appears to be the most promising potential biomarker, responding to both Cu deficiency and excess. The potential for identifying a 'suite' of biomarkers using high-throughput technologies such as transcriptomics and proteomics is only now being examined. A combination of these technologies in conjunction with a range of innovative metal detection techniques is essential if the search for robust copper biomarkers is to be successful.
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PMID:Biomarkers of copper status: a brief update. 1859 83

This study assesses the impact of equine infectious anaemia virus (EIAV) infection on the oxidant/antioxidant equilibrium of horses. Blood samples from 96 Romanian horses aged 1-25 years, were divided into different groups according to their EIAV-infection status, age, and time post-seroconversion. The effect of infection on oxidative stress was estimated by measuring enzymatic antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GPx] and catalase), non-enzymatic antioxidants (uric acid and carotenoids), and lipid peroxidation (malondialdehyde [MDA]). Infection modified the oxidant/antioxidant equilibrium in the horses, influencing GPx and uric acid levels (P<0.05). Time post-seroconversion also contributed to oxidative stress imbalance, exhibiting a significant influence on both SOD and MDA concentrations in the blood (P<0.05). Animal age did not have a significant influence on oxidative stress. Recently infected horses (<1 year following seroconversion), and horses >5 years old, represented the most vulnerable category in terms of oxidative stress, followed by recently infected animals <5 years old. The results of this study are novel in implicating EIAV infection in the development of oxidative stress in horses.
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PMID:Oxidant-antioxidant imbalance in horses infected with equine infectious anaemia virus. 2204 13

Erythropoietin (EPO), used clinically for renal anemia, reportedly exerts beneficial pleiotropic effects in various tissues. Recent studies suggest that nitric oxide (NO) plays an important role in EPO-induced tissue protection. The present study investigated whether recombinant human EPO (rHuEPO) exhibits vasoprotective effects even in the NO synthase-inhibited state. Rats that received a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), in drinking water (0.7 mg/ml) were treated with rHuEPO (75 U/kg, s.c.) three times a week for 2 weeks. The administration of rHuEPO to L-NAME-treated rats had no effect on hematocrit values or increased blood pressure. Vasodilation in response to acetylcholine in the aortic ring was impaired in the L-NAME-treated rats, and improved by rHuEPO. Immunohistochemical staining revealed that infiltration by macrophages and expression of osteopontin were enhanced in the L-NAME-treated rat aorta, and the overexpression was suppressed by rHuEPO. rHuEPO also attenuated medial hyperplasia. Activation of Akt signaling was evident in rHuEPO-treated rats as the increased expression of phosphorylated Akt. rHuEPO enhanced the expression of antioxidant enzymes such as Cu/Zn-superoxide dismutase and heme oxygenase-1 in the aorta. In addition, rHuEPO reduced NADPH oxidase-dependent superoxide production and enhanced the expression of suppressor of cytokine signaling-1(SOCS-1) in the L-NAME-treated rat aorta. These results suggest that a low dose of rHuEPO results in the normalization of endothelial function and vascular inflammation beyond hematopoiesis even in a pharmacologically NO synthase-inhibited state. These effects might be due to the antioxidant properties of rHuEPO. SOCS-1 overexpression would play an important role in suppressing NADPH oxidase activation.
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PMID:Erythropoietin attenuated vascular dysfunction and inflammation by inhibiting NADPH oxidase-derived superoxide production in nitric oxide synthase-inhibited hypertensive rat aorta. 2279 71

The PALB2 protein is associated with breast cancer susceptibility and Fanconi anemia. Notably, PALB2 is also required for DNA repair by homologous recombination (HR). However, the mechanisms that regulate PALB2, and the functional significance of its interaction with the BRCA1 breast cancer susceptibility protein, are poorly understood. Here, to better understand these processes, we fused PALB2, or the PALB2(L21P) mutant which cannot bind to BRCA1, with the BRCT repeats that are present in, and which localize, BRCA1. Our results yield important insights into the regulation of PALB2 function. Both fusion proteins can bypass BRCA1 to localize to sites of DNA damage. Further, the localized fusion proteins are functional, as determined by their ability to support the assembly of RAD51 foci, even in the absence of the capacity of PALB2 to bind BRCA1. Strikingly, the localized fusion proteins mediate DNA double-strand break (DSB)-initiated HR and resistance to mitomycin C in PALB2-deficient cells. Additionally, we show that the BRCA1-PALB2 heterodimer, rather than the PALB2-PALB2 homodimer, mediates these responses. Importantly, we offer the first insight into how BRCA1-dependent recruitment of PALB2 is integrated with other DNA damage signaling pathways. We find that PALB2 localization depends on the presence of MDC1, RNF8, RAP80 and Abraxas upstream of BRCA1. Thus, PALB2 may link HR to a key ubiquitin-related signaling pathway that responds to DSBs.
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PMID:MDC1 and RNF8 function in a pathway that directs BRCA1-dependent localization of PALB2 required for homologous recombination. 2303 82


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