Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used an animal model of extrahepatic biliary obstruction of 7 days' duration to study the production of thiobarbituric acid reactive substances (TBARS), total glutathione (TG), reduced glutathione (GSH), and oxidized glutathione (GSSG), and the enzymatic activities of GSH-peroxidase, GSSG-reductase, and GSH-transferase. Four groups of six rats each were treated with saline, drug solvent, S-adenosyl-L-methionine (SAM) 5 mg/kg/d, subcutaneously, or SAM 10 mg/kg/d, subcutaneously. Extrahepatic biliary obstruction increased TBARS. SAM had the dose-dependent effects of inhibiting TBARS production and increasing TG content, mainly as a result of the increase in GSH. The activity of GSH-peroxidase and GSH-transferase was also significantly increased. In renal tissue these effects were statistically significant only in animals given the higher dose of SAM. In liver we found a reduction in biochemical values indicative of liver damage. We conclude that effect of SAM on hepatorenal function is strongly influenced by the drug's ability to reestablish equilibrium after oxidative tissue stress.
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PMID:Effects of S-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats. 921 60

MX100 is an Escherichia coli K12 genotoxicity tester strain, especially developed for mechanistic studies of chemical mutagens and carcinogens. For the study of the role of specific enzymes in the bioactivation and bioinactivation of carcinogens, it is necessary to characterize MX100 as far as its metabolic bio(in)activation capacities are concerned. In this study such a characterization is performed in two types of cell-free lysates, one derived from stationary phase cells, grown in rich medium (SR-lysates) and one from exponentially growing cells (log phase), cultured in minimal medium (LM-lysates). Six Phase I enzyme activities of aromatic NADPH hydroxylase, NADH hydroxylase, flavin-containing monooxygenase (FMO), nitroreductase, DT-diaphorase and NADPH ferredoxin:oxidoreductase were determined. Activities of six Phase II enzymes glutathione S-transferases (GSTs), N-aryl acetyltransferase (NAT), arylamine sulphotransferase, UDP-glucuronyltransferase and epoxide hydratase and of the Phase III enzyme cysteine conjugate beta-lyase were subsequently assessed. In addition, five antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione (GSH)-reductase, GSH-peroxidase and alkyl hydroperoxide reductase; as well as concentrations of glutathione (GSH) and its disulphide (GSSG), were measured. The activity parameters of all enzymes were compared with those obtained in similar lysates of the Salmonella strain TA100 and in rat liver preparations. The results indicate that MX100 as well as TA100 contain relatively low oxidative but high reductase Phase I activities. Both strains demonstrated low activities for the Phase II conjugation enzymes except for GSTs. In MX100, relatively high activities were detected for all antioxidative enzymes, activities which were lower in TA100. Significant differences in activities were observed between the SR-lysates derived from stationary phase/rich medium and LM-lysates from log phase/minimal medium cells for nitroreductase, GST, SOD, catalase, NADPH ferredoxin:oxidoreductase as well as in GSH content. In general, we described for the first time a metabolic characterization of the E.coli tester strain MX100 and the Salmonella typhimurium strain TA100 and discussed the results in terms of its significance for carcinogen bioactivation and bioinactivation capacities.
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PMID:Characterization of enzyme activities and cofactors involved in bioactivation and bioinactivation of chemical carcinogens in the tester strains Escherichia coli K12 MX100 and Salmonella typhimurium LT2 TA100. 923 69

The filamentous fungus Penicillium chrysogenum showed remarkable resistance to the oxidative stress caused by high concentrations of either hydrogen peroxide (0.35-0.70 M) or tert-butyl hydroperoxide (tert-BOOH, 0.5-2.0 mM), which could be explained well with high levels of glutathione (GSH) peroxidase and catalase activities. The majority of exogenous H2O2 was likely removed by catalase from the cells while tert-BOOH was likely eliminated mainly by the GSH-dependent pathways. The GSH pool decreased considerably at high tert-BOOH concentrations, the glutathione disulphide (GSSG) pool increased at high H2O2 and tert-BOOH concentrations, meanwhile all the peroxide concentrations tested increased markedly the intracellular peroxide concentration. All the enzyme activities taking part in the glutathione metabolism (glutathione peroxidase, glutathione reductase, gamma-glutamyltranspeptidase and glutathione producing activities) except glutathione S-transferase increased significantly after exposing mycelia to both peroxides while the specific glucose-6-phosphate dehydrogenase and catalase activities remained unchanged. In the presence of 0.5 mM diamide both GSSG and GSH concentrations as well as the glutathione reductase and glutathione producing activities were elevated but no significant changes were found in the intracellular peroxide concentration or in any of the other enzyme activities examined.
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PMID:Glutathione metabolism and protection against oxidative stress caused by peroxides in Penicillium chrysogenum. 929 59

Reduced glutathione (GSH) is one of the most preferred biological substrates of myeloperoxidase-derived hypochlorous acid and is a likely target for neutrophil oxidants. We have used HPLC to show that the oxidation of GSH by hypochlorous acid gives two major, stable products in addition to glutathione disulphide (GSSG). The most prevalent product lacks free amine and thiol groups, and was shown by electrospray MS to have a molecular mass of 337 Da. This corresponds to GSH with a gain of two oxygen atoms and a loss of two hydrogen atoms, and is consistent with the product being an internal sulphonamide. The other novel product has a molecular mass of 644 Da, and has amine groups but no free thiols. These properties are consistent with it being glutathione thiolsulphonate. Whereas GSSG in the cell is recycled enzymically, formation of these higher oxidation products is likely to be irreversible. Hypochlorous acid, therefore, could compromise the cell by depleting GSH. The putative sulphonamide may be unique for oxidation by hypochlorous acid and thus provide a useful marker of neutrophil oxidant activity.
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PMID:Characterization of the oxidation products of the reaction between reduced glutathione and hypochlorous acid. 933 54

The effects of citrinin in the maintenance of the homeostasis of the reactive oxygen species in rat liver cells were evaluated. Citrinin (CTN) modifies the antioxidant enzymatic defences of cells through the inhibition of GSSG-reductase and transhydrogenase. No effect was observed on GSH-peroxidase, catalase, glucose 6-phosphate and 6 phosphogluconate dehydrogenases, and superoxide dismutase. The mycotoxin increased the generation of reactive oxygen species, stimulating the production of the superoxide anion in the respiratory chain. The results suggest that oxidative stress is an important mechanism, side by side with other effects previously shown, in the establishment of the cytotoxicity and cellular death provoked by CTN in several tissues.
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PMID:Mechanism of citrinin-induced dysfunction of mitochondria. V. Effect on the homeostasis of the reactive oxygen species. 937 99

In this prospective study the free radical mediated reactions, the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. The patients were randomised into two groups. Group one contained 21 patients treated by open cholecystectomy(OC). Group two consisted of 21 patients treated by laparoscopic cholecystectomy (LC). Both groups had similar patient characteristics. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or other disease were excluded. Values from patients in both groups were compared. The measured biochemical parameters are the following: malondialdehyde (MDA) as a marker of the free radical induced lipid peroxidations, reduced and oxidised glutathione (GSH-GSSG), as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity (MPO) of leukocytes. The results showed significantly lower values of postoperatively measured MDA, GSH-GSSG, and MPO activity of leukocytes in patients with laparoscopic cholecystectomy, indicating a lesser stress response and tissue trauma in this group of patients. The results correspond to the favourable results of most other trials evaluating clinical aspect of LC.
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PMID:Inflammatory mediators and surgical trauma regarding laparoscopic access: free radical mediated reactions. 940 2

The effects of Hg(II) on bioenergetic and oxidative status of rat renal cortex mitochondria were evaluated both in vitro, and in vivo 1 and 24 h after treatment of animals with 5 mg HgCl2/kg i.p. The parameters assessed were mitochondrial respiration, ATP synthesis and hydrolysis, glutathione content, lipid peroxidation, protein oxidation, and activity of antioxidant enzymes. At low concentration (5 microM) and during a short incubation time, Hg(II) uncoupled oxidative phosphorylation while at slightly higher concentration or longer incubation time the ion impaired the respiratory chain. The rate of ATP synthesis and the phosphorylation potential of mitochondria were depressed, although inhibition of ATP synthesis did not exceed 50%. In vivo, respiration and ATP synthesis were not affected 1 h post-treatment, but were markedly depressed 24 h later. ATP hydrolysis by submitochondrial particle FoF1-ATPase was inhibited (also by no more than 50%) both in vitro, and in vivo 1 and 24 h post-treatment. Hg(II) induced maximum ATPase inhibition at about 1 microM concentration but did not have a strong inhibitory effect in the presence of Triton X-100. Oxidative stress was not observed in mitochondria 1 h post-treatment. However, 24 h later Hg(II) reduced the GSH/GSSG ratio and increased mitochondrial lipid peroxidation and protein oxidation, as well as inhibited GSH-peroxidase and GSSG-reductase activities. These results suggest that the following sequence of events may be involved in Hg(II) toxicity in the kidney: (1) inhibition of FoF1-ATPase, (2) uncoupling of oxidative phosphorylation, (3) oxidative stress-associated impairment of the respiratory chain, and (4) inhibition of ATP synthesis.
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PMID:Hg(II)-induced renal cytotoxicity: in vitro and in vivo implications for the bioenergetic and oxidative status of mitochondria. 945 Jun 45

Fotemustine is a relatively novel DNA-alkylating 2-chloroethyl-substituted N-nitrosourea (CENU) drug, clinically used for the treatment of disseminated malignant melanoma in different visceral and non-visceral tissues. Thrombocytopenia has been observed in patients treated with fotemustine and liver and renal toxicities as well. In this study, firstly the metabolism of fotemustine was investigated in vitro and secondly the undesired cytotoxicity of fotemustine as well as different ways of protection against it. In rat hepatocytes, chosen as a model system, fotemustine was shown to cause lactate dehydrogenase (LDH) leakage, glutathione (GSH) depletion, GSSG-formation and lipid peroxidation (LPO). A reactive metabolite, DEP-isocyanate, is most likely responsible for these undesired cytotoxic effects. Based on the observed cytotoxicity mechanisms, chemoprotection with several sulfhydryl-containing nucleophiles and antioxidants was investigated. The sulfhydryl nucleophiles; GSH, N-acetyl-L-cysteine (NAC) and glutathione isopropylester (GSH-IP) protected almost completely against fotemustine-induced LDH-leakage and LPO. NAC and GSH protected partly against fotemustine-induced GSH-depletion. The antioxidant, vitamin E protected completely against fotemustine-induced LPO, but only partly against fotemustine-induced LDH-leakage and not against GSH-depletion. Ebselen, a peroxidase-mimetic organoselenium compound, did not show protective effects against the cytotoxicity of fotemustine, possibly because GSH is required for the bioactivation of ebselen. It is concluded that co-administration of sulfhydryl nucleophiles, in particular NAC and GSH-IP, possibly in combination with antioxidants, such as vitamin E, are effective against the toxicity of fotemustine in vitro. It might, therefore, be worthwhile to investigate the cytoprotective potency of these agents against undesired toxicities of fotemustine in vivo as well.
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PMID:Toxicity of fotemustine in rat hepatocytes and mechanism-based protection against it. 960 83

Myocardial dihydrolipoamide dehydrogenase (LADH) is inactivated after incubation at 30 degree C, with myeloperoxidase (MPO)-dependent systems. The enzyme inactivation was a function of the pro-oxidant system composition and the time of incubation. The standard inactivating system contained 50 mM KH2PO4-K2HPO44, pH 7.4, 0.5-1.0 muM LADH, and pro-oxidant system. After 30 or 60 min of incubation with the MPO/H2O2/NaCl system, LADH inactivation was 64 and 87%, respectively (Figure 1). In the absence of NaCl, inactivation values were 9 and 27%, respectively, whereas in the absence of MPO the inactivation values were 4.0 and 11%, respectively (Figure 1). Under similar experimental conditions, sodium hypochlorite significantly inactivated LADH, thus supporting the role of hipochlorous acid as agent of the MPO/H2O2/CINa system. With the MPO/H2O2/Kl, MPO/H2O2/SCN or the MPO/H2O2/NaNO2 systems LADH inactivation depended on the anion nature, 1-being the most effective (Figure 2). NaNo2 effectively replaced halides as pro-oxidant (Figure 3). The MPO/NADH/halide systems, where NADH replaced H2O2, also inactivated LADH. Native (not denatured) catalase completely prevented the MPO/NADH/Kl system effect (Table 1), in close agreement with H2O2 production by the LADH-catalysed NADH oxidation and the role of H2O2 in LADH inactivation. LADH was also inactivated after incubation with MPO-generated free radicals such as the Chloropromazine and Paracetamol radicals (Table 2). Thiol compounds (Captopril, penicillamine, cysteine, N-acetylcysteine and mercaptopropionylglycine) (Table 3 and Figure 4), as well as taurine, ascorbate (Table 4), GSSG and trypanothione (Figure 5), protected LADH against the MPO-dependent oxidizing systems, and also against NaCIO (Table 4). The summarized observations are discussed in relation to MPO function in free radical production and pathologies such as ischemia-reperfusion injury and inflammation.
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PMID:[Myeloperoxidase as a factor of oxidative damage of the myocardium: inactivation of dihydrolipoamide dehydrogenase]. 970 51

Cellular systems contain as much as millimolar concentrations of both ascorbate and GSH, although the GSH concentration is often 10-fold that of ascorbate. It has been proposed that GSH and superoxide dismutase (SOD) act in a concerted effort to eliminate biologically generated radicals. The tyrosyl radical (Tyr.) generated by horseradish peroxidase in the presence of hydrogen peroxide can react with GSH to form the glutathione thiyl radical (GS.). GS. can react with the glutathione anion (GS-) to form the disulfide radical anion (GSSG-). This highly reactive disulfide radical anion will reduce molecular oxygen, forming superoxide and glutathione disulfide (GSSG). In a concerted effort, SOD will catalyze the dismutation of superoxide, resulting in the elimination of the radical. The physiological relevance of this GSH/SOD concerted effort is questionable. In a tyrosyl radical-generating system containing ascorbate (100 microM) and GSH (8 mM), the ascorbate nearly eliminated oxygen consumption and diminished GS. formation. In the presence of ascorbate, the tyrosyl radical will oxidize ascorbate to form the ascorbate radical. When measuring the ascorbate radical directly using fast-flow electron spin resonance, only minor changes in the ascorbate radical electron spin resonance signal intensity occurred in the presence of GSH. These results indicate that in the presence of physiological concentrations of ascorbate and GSH, GSH is not involved in the detoxification pathway of oxidizing free radicals formed by peroxidases.
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PMID:The fate of the oxidizing tyrosyl radical in the presence of glutathione and ascorbate. Implications for the radical sink hypothesis. 980 66


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