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)

Methionine is a protective factor against various types of liver damage, but excessive dietary methionine is hepatotoxic. Because the mechanisms of L-methionine-related hepatotoxicity are poorly understood, the effect of long-term excessive L-methionine intake on the metabolism of iron and antioxidants was studied in rat liver to determine whether oxidative stress is involved. Wistar male rats were fed either an L-methionine-supplemented (16.0 g/kg) diet or a control diet for 1, 3, 6 and 9 mo. The growth rate of L-methionine-supplemented rats was significantly slower than that of controls. Iron, ferritin and thiobarbituric acid-reactive substances (TBARS) levels in the liver were greater in supplemented rats than in controls. Serum iron and transferrin levels were significantly lower in L-methionine-treated rats compared with controls. Serum ferritin did not differ between the two groups. Hepatic glutathione peroxidase activity, catalase activity and total glutathione concentrations were higher in rats fed the L-methionine-supplemented diet at 1 and 3 mo, but not at 6 and 9 mo. These results indicate that long-term consumption of excess L-methionine by rats may affect primarily iron metabolism rather than the antioxidant defense system and, consequently, induce an accumulation of iron.
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PMID:Long-term consumption of a methionine-supplemented diet increases iron and lipid peroxide levels in rat liver. 1095 34

The in vivo effect of menadione bisulfite adduct on both hepatic oxidative stress and heme oxygenase induction was studied. A marked increase in lipid peroxidation was observed 1 h after menadione bisulfite adduct administration. To evaluate liver antioxidant enzymatic defenses, superoxide dismutase, catalase and glutathione peroxidase activities were determined. Antioxidant enzymes significantly decreased 3 h after menadione bisulfite adduct injection. Heme oxygenase activity appeared 6 h after treatment, peaking 9 h after menadione bisulfite adduct administration. Such induction was preceded by a decrease in the intrahepatic GSH pool and an increase in hydrogen peroxide steady-state concentration, both effects taking place some hours before induction of heme oxygenase. Iron ferritin levels and ferritin content began to increase 6 h after heme oxygenase induction, and these increases were significantly higher 15 h after treatment and remained high for at least 24 h after menadione bisulfite adduct injection. Administration of bilirubin entirely prevented heme oxygenase induction as well as the decrease in hepatic GSH and the increase in lipid peroxidation when administered 2 h before menadione bisulfite adduct treatment. These results indicate that the induction of heme oxygenase by menadione bisulfite adduct may be a general response to oxidant stress, by increasing bilirubin and ferritin levels and could therefore provide a major cellular defense mechanism against oxidative damage.
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PMID:Heme oxygenase induction by menadione bisulfite adduct-generated oxidative stress in rat liver. 1108 16

The mechanism of iron-induced organ failure in iron overload disorders is not known, but it is conjectured that excess iron-catalyzed free radical generation contributes to organ damage. We hypothesized that free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes in plasma, would be significantly increased in non-chelated beta-thalassemia major patients, in comparison to those chelated with either deferiprone (L1) or deferoxamine (desferal). We also report on red cell glutathione peroxidase activity in these patient groups, an enzyme involved in averting the damaging effects of free radicals. Ten patients were chelated with nightly subcutaneous infusions of desferal and 10 received the experimental oral chelator L1. Body iron burden was assessed by serum ferritin and hepatic iron concentrations. In comparison to non-chelated controls, significant decreases of 62% and 64% in total cytotoxic aldehyde concentrations were observed in patients chelated with desferal and L1, respectively (p < 0.001). Significantly lower red cell glutathione peroxidase activity was also observed in non-chelated controls, in comparison to those chelated with either desferal or L1 (p < 0.001). This is the first report on the concentrations of cytotoxic aldehydes in non-chelated beta-thalassemia major patients, and the first to report on the effects of L1 against cytotoxic aldehyde formation in plasma of patients with iron-overload.
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PMID:Erythropoiesis: Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelated with Deferoxamine or Deferiprone (L1) Versus NO Chelation. 1139 54

This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation or cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (CSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters-GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.
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PMID:Oxidative stress in heart tissue of hyperthyroid and iron supplemented rats. 1173

In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions.
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PMID:Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. 1177 98

Cellular oxidative stress is due to the production of reactive oxygen species (ROS), on the one hand, and weaknesses of the antioxidative defence, on the other. This is particularly true for cells with an active metabolism such as neurons and muscle cells, but it is also relevant for all other cell types. Hydrogen peroxide is an important member of ROS and is generated predominantly by mitochondria. In combination with reduced trace metals such as iron or copper, hydrogen peroxide is transformed into the highly reactive hydroxyl radical which causes damage to virtually all macromolecules. Oxidation of nucleic acids results in mutations while protein denaturation leads to enzyme defects and impairment of the cytoskeleton. Lipid peroxidation in cell membranes is strongly involved in the perturbation of ion homeostasis. Because this cell damage ultimatively causes cell death, oxidative stress initiates several diseases. Mitochondria play a major role in this context because they are the main source of endogenous oxidative stress and additionally function as an inducer of programmed cell death (apoptosis). Several strategies of antioxidative defence exist: While transition metals can be inactivated by chelating proteins (e.g., ferritin), ROS can be reduced enzymatically (e.g., by the glutathione peroxidase) or non-enzymatically by antioxidants (e.g., by vitamin E, vitamin C and glutathione). Stress proteins are implicated in the repair and transport of denatured proteins as well as in the inhibition of apoptosis.
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PMID:[Oxidative stress, age-dependent [correction of age-related] cell damage and antioxidative mechanisms]. 1208 May 77

Electrophiles formed during metabolic activation of chemical carcinogens and reactive oxygen species generated from endogenous and exogenous sources play a significant role in carcinogenesis. Cancer chemoprevention by induction of phase 2 proteins to counteract the insults of these reactive intermediates has gained considerable attention. Nuclear factor E2 p45-related factor 2 (Nrf2), a bZIP transcription factor, plays a central role in the regulation (basal and or inducible expression) of phase 2 genes by binding to the "antioxidant response element" in their promoters. Identification of novel Nrf2-regulated genes is likely to provide insight into cellular defense systems against the toxicities of electrophiles and oxidants and may define effective targets for achieving cancer chemoprevention. Sulforaphane is a promising chemopreventive agent that exerts its effect by strong induction of phase 2 enzymes via activation of Nrf2. In the present study, a transcriptional profile of small intestine of wild-type (nrf2 +/+) and knock out (nrf2 -/-) mice treated with vehicle or sulforaphane (9 micromol/day for 1 week, p.o.) was generated using the Murine Genome U74Av2 oligonucleotide array (representing approximately 6000 well-characterized genes and nearly 6000 expressed sequence tags). Comparative analysis of gene expression changes between different treatment groups of wild-type and nrf2-deficient mice facilitated identification of numerous genes regulated by Nrf2 including previously reported Nrf2-regulated genes such as NAD(P)H:quinone reductase (NQO1), glutathione S-transferase (GST), gamma-glutamylcysteine synthetase (GCS), UDP-glucuronosyltransferases (UGT),epoxide hydrolase, as well as a number of new genes. Also identified were genes encoding for cellular NADPH regenerating enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme), various xenobiotic metabolizing enzymes, antioxidants (glutathione peroxidase, glutathione reductase, ferritin, and haptaglobin), and biosynthetic enzymes of the glutathione and glucuronidation conjugation pathways. The data were validated by Northern blot analysis and enzyme assays of selected genes. This investigation expands the horizon of Nrf2-regulated genes, highlights the cross-talk between various metabolic pathways, and divulges the pivotal role played by Nrf2 in regulating cellular defenses against carcinogens and other toxins.
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PMID:Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. 1223 84

The speciation of trace elements in serum samples of hemodialysed patients was investigated using on-line connection of SEC and ICP-MS. The 0.02 mol/l TRIS-HCl buffer of pH 7.5 was used as mobile phase. The results of speciation as well as the total concentration data were compared with those of control group of healthy person. Alterations of total concentration were observed in case of selenium and zinc only. Iron was present in form of transferrin and ferritin, main amount of copper was bound to ceruloplasmin and selenium compounds were identified as selenoproteine P and glutathione peroxidase. The latter compound was detected in samples of control group only. The chromatograms of the other elements were similar and no substantial changes between both investigated groups were observed.
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PMID:Speciation of Cu, Se, Zn and Fe in blood serum of hemodialysed patients. 1244 34

The aim of this work was to describe the factors influencing the levels of three antioxidant markers -total antioxidant status, erythrocyte copper/zinc superoxide dismutase (SOD), whole-blood selenium glutathione peroxidase--and to establish their reference intervals in supposedly healthy subjects. The studied population included 463 subjects, i.e., 223 adults and 140 children aged 20 to 65 and 4 to 19 years, respectively. The effect of factors such as age, gender, body mass index, alcohol and tobacco consumption, menopause, drug intake, trace elements, transferrin, ferritin, albumin, bilirubin, haptoglobin, total proteins, uric acid, haemoglobin, and mean corpuscular volume of erythrocytes have been studied for the three antioxidant markers. Total antioxidant status (TAS) was higher in men than in women whatever the age (p < 0.001). Albumin and uric acid in men, women and girls, and total proteins in boys were significant determinants of TAS levels. Mean corpuscular volume of erythrocytes were negatively and significantly associated with SOD activity in men and in women (p < 0.01) but not in children. Among the studied determinants, none were found to influence the selenium glutathione peroxidase activity in the four groups. Reference intervals including the 90% confidence intervals were established by age and sex for the three antioxidant markers.
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PMID:Serum total antioxidant status, erythrocyte superoxide dismutase and whole-blood glutathione peroxidase activities in the Stanislas cohort: influencing factors and reference intervals. 1266 9

Iron-deficiency anemia has been shown to alter body mineral concentrations and activities of iron- and non-iron-containing enzymes, especially those with antioxidant functions. These effects, however, have been less studied in nonanemic iron-depleted individuals. Thus, this study assessed indices of selenium status in 12 college-aged females with adequate iron stores and 15 college-aged females with low iron stores before and after iron therapy. Blood samples were drawn at baseline for both groups and following iron supplementation in the low-iron-stores group. Hematocrit, hemoglobin, and serum ferritin concentrations of the low iron- stores group were significantly lower than those of the control group. The serum transferrin receptor-to-serum ferritin ratio in the low-iron stores group was significantly greater than that of the control group. Serum selenium and glutathione peroxidase concentrations of the low-iron-stores group were not significantly different from those of the controls. Iron supplementation significantly increased hemoglobin, hematocrit, and serum ferritin concentrations and significantly decreased the serum transferrin receptor concentration and serum transferrin receptor:serum ferritin ratio in the low-iron-stores group posttreatment compared to pretreatment. Serum selenium and glutathione peroxidase concentrations did not differ significantly from pretreatment to posttreatment in the low-iron-stores group. Results of this study indicate that low iron stores without anemia are not associated with impaired selenium status in college-aged females.
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PMID:Iron depletion without anemia is not associated with impaired selenium status in college-aged women. 1271 7


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