Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of rats with nifurtimox, a nitrofuran derivative widely used for the treatment of Chagas' disease, induced a time- and dose-dependent depletion of liver glutathione, maximal effects being obtained with 200 mg nifurtimox/kg body weight. Extra release of both oxidized (GSSG) and reduced (GSH) glutathione into bile contributed to this depletion. Glutathione excretion into bile accounted for only part of liver glutathione loss, thus indicating that, in addition to the GSH-peroxidase reaction (resulting in GSSG generation), other glutathione-related processes were involved in nifurtimox detoxification. Bile flow, bile salt excretion, liver lipid conjugated diene content, liver glutathione reductase and glutathione peroxidase activities, and serum alanine aminotransferase (ALAT) activity were not affected by the nifurtimox treatment, thus ruling out widespread damage of the liver cell by nifurtimox. Nevertheless, the extra GSH release in the nifurtimox-treated rats may indicate an alteration of the hepatocyte membrane.
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PMID:Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment. 684 98

Human erythrocytes were separated into three groups according to their density and age by centrifugation in a continuous Percoll gradient. The specific activities of glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, glutathione reductases as well as the glutathione and selenium content were highest in the youngest cell and uniformly decreased by about 20-30% in the eldest group. The age-dependence of superoxide dismutase was much more pronounced. The malondialdehyde content taken as an estimate for lipid peroxidation showed an inverse age dependence and increased by 35% in the eldest cell population. Red blood cells from 10 anemic patients exhibited less glutathione and also less malondialdehyde, while GSH-peroxidase and GSSG-reductase contents were higher. The parameters showed similar age profiles as in healthy subjects. The findings support the concept of lipid peroxidation as one of the causal events in red cell aging, but do not allow to deduce the involvement of a single enzyme related to the glutathione redox cycle in this process.
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PMID:[Activity of the glutathione redox system in human erythrocytes at various ages]. 713 38

The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of cisplatin ototoxicity: antioxidant system. 747 81

In an attempt to assess the possible oxidative stress associated with the transient exercise-induced activation of polymorphonuclear neutrophils (PMN), we compared the effects of eccentric and concentric exercises (downhill run: DR and uphill walk: UW, respectively) of equal duration (35 min) and similar energy cost (60% VO2max) on plasma levels of ascorbic acid ([AA]) and blood concentration of reduced ([GSH]) and oxidized ([GSSG]) glutathione. Eight healthy male subjects took part in this study. Plasma concentration of myeloperoxidase ([MPO]) was used as a specific marker of PMN activation. While there were no significant changes in [MPO] and [AA] in UW experiments, [MPO] increased (+80%) and [AA] decreased significantly during DR tests (P < 0.01 and P < 0.05, respectively). A significant negative relationship was observed between [AA] and [MPO] in DR experiments only (r = -0.49; P < 0.01). Mean (+/- SEM) basal GSH and GSSG concentrations, calculated by pooling the values measured before both tests, were 0.54 +/- 0.02 and 0.12 +/- 0.007 mM, respectively. The blood concentration of these compounds remained practically unchanged in both exercise tests. These results confirm the role played by the eccentric component of muscle contraction in transient exercise-induced PMN activation and suggest that this activation was partly involved in the decrease in [AA] observed in DR experiments. The oxidant stress associated with the exercise protocol used in this study was insufficient to alter blood levels of reduced and oxidized glutathione.
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PMID:Blood levels of reduced/oxidized glutathione and plasma concentration of ascorbic acid during eccentric and concentric exercises of similar energy cost. 751 36

Metallothionein (MT) in tumor cells has been implicated as one of the factors involved in mechanisms of resistance to anti-cancer drugs, including cis-diaminedichroloplatinum (CDDP) and adriamycin (ADM). The relationship between the expression of MT and chemotherapy with anti-cancer drugs was studied in CDDP- and ADM-resistant human bladder cancer cell lines and tissue samples from clinical cases. In drug-resistant cell lines (T-24/ADM, CI-7/CDDP) established in our laboratory, MT expression was studied by immunohistochemistry using the avidin-biotin peroxidase complex (ABC) method and radioimmunoassay (RIA), using anti-MT antibody. In addition, other potential mechanisms of drug resistance, such as P-glycoprotein expression were examined and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione-S-transferase (GST) determined in these cell lines. The results of these investigations demonstrate that the expression of MT in resistant cell lines increased 2.1- and 2.5-fold when compared with parent cell lines (CI-7, T-24). GSH, GSSG and GST levels were unchanged and P-glycoprotein was not over-expressed. A total of 120 tissue samples from 35 clinical cases of bladder cancer, before and after chemotherapy, were stained for MT which was detected in 10 of the 35 cases before chemotherapy. The incidence of MT expression was significantly higher (p < 0.05) in cases with lower pathological tumor grades.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Over-expression of metallothionein and drug-resistance in bladder cancer. 762 49

The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG), the glutathione reductase catalysed reaction (GSSG-->2GSH), or both. Neonatal rat heart cell cultures were subjected to a standardized protocol of oxidative stress using 80 mumol.l-1 cumene hydroperoxide (CHPO) for 0-90 min. The consequences of this protocol were described in terms of cellular concentrations of GSH, GSSG, NADPH and ATP, formation of malondialdehyde (MDA), release of GSSG and of ATP catabolites, depression of contraction frequency, cellular calcium overload, and enzyme release. Trolox-C, an analogue of vitamin E, accelerated the glutathione peroxidase reaction leading to lowering of GSH concentration and the GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, delayed calcium overload, and less enzyme release. Glucose was used to accelerate the glutathione reductase reaction by supplying NADPH, leading to higher GSH concentration and a higher GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, unchanged development of calcium overload, and less enzyme release. As a full turn of the glutathione redox cycle involves both the peroxidase and the reductase reactions, the combination of Trolox-C and glucose was superior to either of the two alone: 90 min following addition of CHPO together with Trolox-C and glucose, the GSH concentration and the GSH/GSSG ratio were almost normal, MDA formation was extremely low, calcium overload was markedly delayed, and enzyme release hardly occurred at all. Cells remained beating in the observation period of 30 min. We conclude that the capacity of the glutathione redox cycle to withstand oxidative stress can be increased by stimulation of either the peroxidase reaction or the reductase reaction, and that optimal redox cycling is achieved by stimulation of both reactions.
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PMID:Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle. 767 3

Red blood cells and plasma reduced and oxidized glutathione levels, glutathione peroxidase (GSH-Px) activity, thiobarbituric acid reactants (TBAR) of both chronic ambulatory peritoneal dialysis (CAPD) patients and a matched control group were investigated in this study. Oxidized and reduced pyridinic nucleotides in red blood cells (RBC), in which NADPH is a direct expression of hexose monophosphate shunt function, were also studied. The results obtained indicate that RBC and plasma are exposed to oxidative stress in CAPD. This condition is characterized by a decreased GSH/GSSG ratio, particularly evident in RBC as a consequence of the GSSG accumulation. Lipid peroxidation is increased, as indicated by raised TBAR levels, and reduced pyridinic nucleotides are decreased. Increased GSH-Px levels and unmodified or slightly increased GSH content were observed in the RBC but not in plasma, which showed decreased GSH and unmodified peroxidase activity. Peroxidase correlated positively with TBAR levels in the RBC lysates. In a subgroup of patients treated with erythropoietin (vs. untreated patients and controls) no differences were observed in the glutathione-related parameters studied. These data suggest that a mechanism for adaptation to oxidative conditions may be present in CAPD and its effects on RBC integrity are discussed in comparison with the hemodialysis conditions previously studied.
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PMID:Redox state, antioxidative activity and lipid peroxidation in erythrocytes and plasma of chronic ambulatory peritoneal dialysis patients. 775 12

Gastric peroxidase (GPO) was purified to apparent homogeneity to characterize its major physiological electron donor. The enzyme (RZ = 0.7), with a subunit molecular mass of 50 kDa, is a glycoprotein, with a relative abundance of aspartic and glutamic acid over arginine and lysine. It has a Soret maximum at 412 nm, which is shifted to 426 nm by H2O2 due to formation of compound II. Although the physiological electron donors I-, Br- and SCN-, but not Cl-, are oxidized by GPO optimally at acid pH, only I- and SCN- are oxidized appreciably at physiological pH. Considering that the I- concentration in stomach is less than 1 microM, whereas the SCN- concentration is about 250 microM, SCN- may act as a major electron donor for GPO. Moreover, SCN- oxidation remains unaltered in the presence of physiological concentrations of other halides. The second-order rate constant for the reaction of GPO with H2O2 (k1) and compound I with SCN- (k2) at pH 7 was found to be 8 x 10(7) M-1.s-1 and 2 x 10(5) M-1.s-1 respectively. GPO has significant pseudocatalase activity also in the presence of I- or Br-, but it is blocked by SCN-. The SCN- oxidation product OSCN- may be reduced back to SCN- by cellular GSH, and GSSG may be reduced back to GSH by glutathione reductase and NADPH. In a system reconstituted with pure glutathione reductase, NADPH, GSH, SCN- and H2O2. GPO-catalysed SCN- oxidation could be coupled to NADPH oxidation. This system where GPO utilizes SCN- as the major physiological electron donor may operate efficiently to scavenge intracellular H2O2.
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PMID:Thiocyanate, a plausible physiological electron donor of gastric peroxidase. 782 54

A comprehensive study was performed on the brains of various vertebrate species showing different life energy potentials in order to find out if free radicals are important determinants of species-specific maximum life span. Brain superoxide dismutase, catalase, Se-dependent and independent GSH-peroxidases, GSH-reductase, and ascorbic acid showed significant inverse correlations with maximum longevity, whereas GSH, uric acid, GSSG/GSH, in vitro peroxidation (thiobarbituric acid test), and malondialdehyde (measured by HPLC), did not correlate with maximum life span. Superoxide dismutase, catalase, GSH-peroxidase, GSH and ascorbate results agree with those previously reported in various independent works using different animal species. GSSG/GSH, and true malondialdehyde (HPLC) results are reported for the first time in relation to maximum longevity. The results suggest that longevous species simultaneously show low antioxidant concentrations and low levels of in vivo free radical production (a low free radical turnover) in their tissues. The "free radical production hypothesis of aging" is proposed: a decrease in oxygen radical production per unit of O2 consumption near critical DNA targets (mitochondria or nucleus) increases the maximum life span of extraordinarily long-lived species like birds, primates, and man. Free radical production near these DNA sites would be a main factor responsible for aging in all the species, in those following Pearl's (Rubner's) metabolic rule as well as in those not following it.
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PMID:A decrease of free radical production near critical targets as a cause of maximum longevity in animals. 795 69

Furazolidone (F) and its 5-nitrofuran derivatives, occasionally used in veterinary and human medicine, are active against some microorganisms. This drug is considered to be mutagenic in special bacterial test systems. For public health reasons, the presence of F and other 5-nitrofuran residues in edible mammalian and poultry tissues is strictly prohibited. One-month-old experimental chickens (n = 2 x 25) were fed 300 mg.kg-1 furazolidone for 3 days. A separate subgroup (n = 11) was used for monitoring the kinetics of F in the blood plasma. Liver, lung and blood plasma samples taken from the experimental and control chickens after treatment were tested for glutathione-peroxidase (GSH-Px), glutathione reductase (GSH-R), catalase (CAT), superoxide dismutase (SOD) activities, reduced and oxidized glutathione (GSH and GSSG), malondialdehyde (MDA), alpha-tocopherol (vE), selenium (Se) and F concentrations. On post-treatment day 2, SOD activity was significantly lowered in the liver only. GSH-Px did not show any characteristic change in any of the tissues. CAT and GSH-R activities were significantly reduced in both organs until post-treatment day 5. At the same time, a significant decrease of GSH accompanied by an increase in GSSG concentration, was found in both tissues. Oral F treatment produced a transient increase in lipid peroxidation levels measured by the formation of MDA. Alpha-tocopherol content significantly decreased in both organs by post-treatment day 2. Se concentrations showed an insignificant rate of decrease. F concentration in the blood plasma reached its peak already 30 min after treatment. In the liver and lungs, F decreased sharply, reaching the detection limit between days 2-5 after treatment. Furazolidone administered per os was found to alter the in vivo antioxidative enzymatic defense mechanisms. Increased lipid peroxidation and the concomitant oxidative stress may affect the functional integrity of the tissues.
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PMID:Contribution to the pathobiochemistry of furazolidone-induced oxidative toxicity in chickens. 811 90


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