Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human skin chronically exposed to UV light is known to accumulate iron and to have an increased ferritin content as compared to unexposed areas. Iron accumulation is also found in many inflammatory skin diseases. Cultured human fibroblasts loaded with iron by incubation with non-toxic concentrations of the ferric nitrilotriacetate complex have been irradiated with low (up to 15 J/cm2) and moderate (up to 45 J/cm2) UVA doses. At low irradiation doses, lipid peroxidation doubles without affecting the viability of iron-loaded cells. At higher irradiation doses (30 J/cm2) the photocytotoxicity of UVA towards iron-loaded cells increases in a concentration-dependent manner with the iron load. Thus, after exposure to 30 J/cm2 of UVA, the cytotoxicity is about 3-fold greater for cells incubated for 75 min with 100 microM of the ferric complex as compared to those not treated with the ferric complex. Incubation with desferrioxamine, an extremely efficient chelator of ferric ion or vitamin E, a radical scavenger which blocks the lipid peroxidation radical chain, leads to marked inhibition of the sensitizing effects of iron on lipid peroxidation but is less effective for the survival of cells exposed to UVA. A similar concentration-dependent protective effect of desferrioxamine was observed with cultured fibroblasts not treated with the ferric complex. It is suggested that the photoreduction of ferritin and/or other iron-containing proteins plays a significant role in the UVA-induced photocytotoxicity of skin fibroblasts.
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PMID:Sensitization of skin fibroblasts to UVA by excess iron. 910 24

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.
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PMID:Increased oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C. 926 Dec 77

We describe a 4-year-old girl with a spontaneous blistering disorder that was consistent with porphyria cutanea tarda (PCT). There was no familial history of the disease or any obvious causative factors present. Oral hydroxychloroquine (3 mg/kg) was given twice weekly along with vitamin E (200 U/d) as an antioxidant. Within 6 weeks, marked decreased blistering occurred and by 12 weeks no blistering was evident. Despite clinical improvement and tolerance of hydroxychloroquine, urinary uroporphyrin, aspartate aminotransferase, and ferritin levels continued to rise reaching peak levels at 16 weeks of therapy. Near total biochemical remission was observed at 40 weeks and all therapy was discontinued at 60 weeks.
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PMID:Childhood-onset porphyria cutanea tarda: successful therapy with low-dose hydroxychloroquine (Plaquenil). 959 92

We investigated the oxidative state of low-density lipoprotein (LDL) in patients with beta-thalassemia to determine whether there was an association with atherogenesis. Conjugated diene lipid hydroperoxides (CD) and the level of major lipid antioxidants in LDL, as well as modified LDL protein, were evaluated in 35 beta-thalassemia intermedia patients, aged 10 to 60, and compared with age-matched healthy controls. Vitamin E and beta-carotene levels in LDL from patients were 45% and 24% of that observed in healthy controls, respectively. In contrast, the mean amount of LDL-CD was threefold higher and lysil residues of apo B-100 were decreased by 17%. LDL-CD in thalassemia patients showed a strong inverse correlation with LDL vitamin E (r = -0.784; P <.0001), while a negative trend was observed with LDL-beta-carotene (r = -0.443; P =.149). In the plasma of thalassemia patients, malondialdehyde (MDA), a byproduct of lipid peroxidation, was increased by about twofold, while vitamin E showed a 52% decrease versus healthy controls. LDL-CD were inversely correlated with plasma vitamin E (r = -0.659; P <.0001) and correlated positively with plasma MDA (r = 0.621; P <. 0001). Plasma ferritin was positively correlated with LDL-CD (r = 0.583; P =.0002). No correlation was found between the age of the patients and plasma MDA or LDL-CD. The LDL from thalassemia patients was cytotoxic to cultured human fibroblasts and cytotoxicity increased with the content of lipid peroxidation products. Clinical evidence of mild to severe vascular complications in nine of the patients was then matched with levels of LDL-CD, which were 36% to 118% higher than the mean levels of the patients. Our results could account for the incidence of atherogenic vascular diseases often reported in beta-thalassemia patients. We suggest that the level of plasma MDA in beta-thalassemia patients may represent a sensitive index of the oxidative status of LDL in vivo and of its potential atherogenicity.
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PMID:Oxidative modification of low-density lipoprotein and atherogenetic risk in beta-thalassemia. 980 87

This study was designed to examine the interactions among dietary iron (Fe), copper (Cu), and zinc (Zn) and their effects on Fe status and oxidative stress in female rats. In a three-factor central composite response surface design, rats were assigned to 15 groups and fed modified AIN-93G basal diets with varying amounts of Fe and Zn (7.0, 15.5, 45.8, 135.6, or 300 micrograms/g diet) and Cu (0.5, 1.1, 3.2, 9.2, or 20 micrograms/g diet) for 6 wk. Variations in hemoglobin, hematocrit, and serum ferritin were mainly related to dietary Fe. Liver nonheme Fe was directly affected by dietary Fe and was slightly attenuated by interactions between Cu and Zn, and Zn and Fe. Serum ceruloplasmin activity was primarily determined by an interaction between Cu and Zn with substantial moderation by the quadratic effect of dietary Cu. Liver and heart total superoxide dismutase (SOD) and Cu/Zn SOD activities were directly affected by dietary Cu. Dietary Fe was the only significant, yet weak, predictor of liver thiobarbituric acid reactive substances (TBARS) and vitamin E content and serum triacylglycerols. Variability in serum Cu was mostly determined by the interaction between Cu and Fe, with modification from the quadratic effect of dietary Cu. Serum Zn varied with dietary Zn with a small negative influence from the interaction between Cu and Fe. In summary, Fe status was minimally influenced by dietary Zn or Cu, and Fe intakes 10-fold greater than required did not induce overt oxidative stress in female rats. In addition, measures of antioxidant capacity were primarily influenced by dietary Cu and were optimal at moderate intakes of this micronutrient.
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PMID:Dietary copper primarily affects antioxidant capacity and dietary iron mainly affects iron status in a surface response study of female rats fed varying concentrations of iron, zinc and copper. 1039

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.
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PMID:Blood antioxidant status and urinary levels of catecholamine metabolites in beta-thalassemia. 1040 Apr 57

The invention of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia was a hallmark in the care of patients with renal insufficiency. Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl. Normalizing haemoglobin levels may reduce morbidity and mortality and improve quality of life in haemodialysis patients. During long-term treatment, most patients will not respond adequately to therapy with rHuEpo alone. The most important confounding factor, limiting the effectiveness of rHuEpo, is absolute or functional iron deficiency, which is now recognized and treated in many dialysis units. However, there are several other adjuvant treatment options which may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3 mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome functional iron deficiency in patients with high ferritin levels. The potential increase of oxidative stress induced by intravenous iron therapy may be blunted by concomitant administration of vitamin E (1200 IU). There is clear evidence from the literature that treatment of secondary hyperparathyroidism by vitamin D improves erythropoiesis. The most recently discovered biological effects of rHuEpo include the induction of several genes in endothelial cells as well as a role for erythropoietin in the outcome of plasmodium infection. A new erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP), which is as effective and safe as rHuEpo, with the potential advantage of less frequent dosing.
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PMID:Novel aspects of erythropoietin response in renal failure patients. 1150 83

Our aim was to show, in continuous ambulatory peritoneal dialysis (CAPD) patients, the relationships between zinc (serum level and dietary intake) and adequacy and duration of CAPD, age, and measures of nutrition. Serum zinc (12.2 +/- 1.8 mumol/L) was not significantly related to dietary zinc intake (9.9 +/- 2.5 mg daily), but depended on daily instilled (r = -0.331, p < 0.05) and effluent (r = -0.311, p < 0.05) dialysate volumes and on patient age (r = -0.304, p < 0.05). Positive correlations were seen between serum zinc level and laboratory (but not anthropometric) markers of nutrition: prealbumin (r = 0.349, p < 0.05), iron (r = 0.447, p < 0.05), transferrin saturation [(TSAT) r = 0.374, p < 0.05]. Additionally, zinc intake was positively related to serum ferritin level (r = 0.370, p < 0.05). Serum zinc level positively influenced blood morphology [correlation with hemoglobin (r = 0.287, p < 0.05) and mean corpuscular hemoglobin concentration (r = 0.361, p < 0.05)]. Zinc intake showed negative correlations with serum levels of total cholesterol (r = -0.373, p < 0.05) and vitamin E (r = -0.504, p < 0.05), and a positive correlation with HDL: total cholesterol ratio (r = 0.338, p < 0.05). Mean values of three latter parameters were out of the normal limits (total cholesterol: 219.2 +/- 47.0 mg/dL; vitamin E: 1.91 +/- 0.82 mg/dL; HDL: total cholesterol ratio: 16.7 +/- 5.1). We conclude that, in CAPD patients, zinc is a marker of nutrition showing beneficial effect on serum iron parameters, blood morphology, lipid profile, and elevated vitamin E concentration. Zinc supplementation is needed for approximately 16% of CAPD patients, especially older patients and those requiring higher dialysate volumes.
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PMID:Zinc as a marker of nutrition in continuous ambulatory peritoneal dialysis patients. 1151 Feb 81

Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals, thereby reducing cardiovascular disease risk. The primary purpose was to determine the effect of soy protein (40 g/d) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We also determined the contribution of coagulation and fibrinolytic and other factors (e.g., body size and composition; serum estrogens, ferritin, iron; dietary intake) to lipid profiles. Subjects were randomly assigned to treatment: isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n = 21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12 and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24. Coagulation and fibrinolytic factors were not adversely affected by treatment. Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or in all subjects combined. Time significantly (P < 0.001) affected serum total cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations. We could not attribute changes over time to various factors, but at baseline accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for 50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E and % energy from fat had positive effects, whereas plasma plasminogen activator inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids. The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women.
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PMID:Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. 1153 67

Free radicals and other so-called 'reactive species' are constantly produced in the brain in vivo. Some arise by 'accidents of chemistry', an example of which may be the leakage of electrons from the mitochondrial electron transport chain to generate superoxide radical (O2*-). Others are generated for useful purposes, such as the role of nitric oxide in neurotransmission and the production of O2*- by activated microglia. Because of its high ATP demand, the brain consumes O2 rapidly, and is thus susceptible to interference with mitochondrial function, which can in turn lead to increased O2*- formation. The brain contains multiple antioxidant defences, of which the mitochondrial manganese-containing superoxide dismutase and reduced glutathione seem especially important. Iron is a powerful promoter of free radical damage, able to catalyse generation of highly reactive hydroxyl, alkoxyl and peroxyl radicals from hydrogen peroxide and lipid peroxides, respectively. Although most iron in the brain is stored in ferritin, 'catalytic' iron is readily mobilised from injured brain tissue. Increased levels of oxidative damage to DNA, lipids and proteins have been detected by a range of assays in post-mortem tissues from patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, and at least some of these changes may occur early in disease progression. The accumulation and precipitation of proteins that occur in these diseases may be aggravated by oxidative damage, and may in turn cause more oxidative damage by interfering with the function of the proteasome. Indeed, it has been shown that proteasomal inhibition increases levels of oxidative damage not only to proteins but also to other biomolecules. Hence, there are many attempts to develop antioxidants that can cross the blood-brain barrier and decrease oxidative damage. Natural antioxidants such as vitamin E (tocopherol), carotenoids and flavonoids do not readily enter the brain in the adult, and the lazaroid antioxidant tirilazad (U-74006F) appears to localise in the blood-brain barrier. Other antioxidants under development include modified spin traps and low molecular mass scavengers of O2*-. One possible source of lead compounds is the use of traditional remedies claimed to improve brain function. Little is known about the impact of dietary antioxidants upon the development and progression of neurodegenerative diseases, especially Alzheimer's disease. Several agents already in therapeutic use might exert some of their effects by antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone.
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PMID:Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. 1159 35


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