Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rough and smooth microsomes of brain in senescent rats showed less sensitivity to ascorbate-, NADPH- and cumene hydroperoxide-induced peroxidative damage compared with those of young adults. The observed decrease in peroxidative potential in senescent rats seemed to be due to decrease in the substrate for peroxidation in the form of phospholipids and increase in the level of antioxidants such as reduced glutathione and superoxide dismutase.
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PMID:Decreased peroxidative potential in rat brain microsomal fractions during ageing. 250 96

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
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PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

The glutamine synthetase and the NADP-specific glutamate dehydrogenase activities of Neurospora crassa were lost in a culture without carbon source only when in the presence of air. Glutamine synthetase was previously reported to be liable to in vitro and in vivo inactivation by activated oxygen species. Here we report that NADP-specific glutamate dehydrogenase was remarkably stable in the presence of activated oxygen species but was rendered susceptible to oxidative inactivation when chelated iron was bound to the enzyme and either ascorbate or H2O2 reacted on the bound iron. This reaction gave rise to further modifications of the enzyme monomers by activated oxygen species, to partial dissociation of the oligomeric structure, and to precipitation and fragmentation of the enzyme. The in vitro oxidation reaction was affected by pH, temperature, and binding to the enzyme of NADPH. Heterogeneity in total charge was observed in the purified and immunoprecipitated enzymes, and the relative amounts of enzyme monomers with different isoelectric points changes with time of the oxidizing reaction.
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PMID:Oxidation of Neurospora crassa NADP-specific glutamate dehydrogenase by activated oxygen species. 253 Feb 8

Feeding rats with 4 g/kg body weight of sardine oil during 7 or 14 days increases the content of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte and hepatic microsomal membranes by 2 to 6%. These membranes show increased susceptibility to the induction of oxidative stress, expressed as lipid peroxidation, when they are exposed to Fe2+-ascorbate and to NADPH-FE3+-ADP, respectively. The results indicate that in order to prevent the increased susceptibility to lipid peroxidation, supplementation with larger amounts of antioxidants may be needed than those required to stabilize the oil.
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PMID:Ingestion of high doses of fish oil increases the susceptibility of cellular membranes to the induction of oxidative stress. 255 51

1. The major components of hepatic drug biotransformation system were identified in a Brazilian freshwater benthic fish. 2. Cytochrome P-450 difference spectra were obtained adding 0.02 mM phenazine ethosulphate and 2 mM ascorbate to microsomal suspensions. Basal levels of P-450 were high (0.9 nmol/mg of microsomal protein) and were not induced by 3-MC. 3. Microsomal NADPH-cytochrome C reductase activity was determined in presence of 1.3 x 10(-4) M NADPH, 3.3 x 10(-5) M cytochrome C, 1.0 x 10(-4) M EDTA, 66 micrograms of microsomal protein per ml in a 0.3 M Tris-HCl buffer, pH 8.6. Basal levels of NADPH-cytochrome C were 152.7 nmoles/min/mg of microsomal protein.
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PMID:Drug metabolism components in liver microsomes from Hypostomus punctatus, a Brazilian benthic fish (Cascudo). 257 96

As shown by accumulation of malonic dialdehyde and chemiluminescence rate monitoring tetracycline activated both NADPH- and ascorbate-dependent lipid peroxidation in liver tissue of 1, 3, 12 and 24 months old rats. The most distinct induction of lipid peroxidation was observed in old animals, which appears to occur due to a decrease in efficiency of NADPH-GSH-dependent enzymatic antioxidant system. Silibore prevented the stimulating effect of tetracycline on enzymatic and nonenzymatic lipid peroxidation, being apparently involved in hepatoprotective effect.
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PMID:[The effect of tetracycline and silibore on lipid peroxidation in the liver od rats of various age]. 261 36

The protective role of the glutathione system against oxidative stress was studied in the model of Fe2+/ascorbate induced peroxidation in isolated rat liver mitochondria. There was a successive diminution of the mitochondrial glutathione pool, essentially due to losses of the reduced form (GSH) during the initiation phase of peroxidation, while the redox state of glutathione was not influenced significantly before the onset of massive malondialdehyde formation. Oxidizable substrates such as glutamate/malate and 3-hydroxybutyrate affected peroxidation by extending the period of the induction phase. Obviously that was due to the supply of NADPH to recover GSH via GSSG-reductase as evidenced by the parallel decline of the NADP(H) and the glutathione-system redox states. Although the data strongly support the fact that mitochondrial glutathione plays a central role in the defence against oxidative stress, there are, under special conditions of a high succinate supply, other potent defence systems in isolated mitochondria.
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PMID:The role of mitochondrial glutathione in the defence against Fe2+/ascorbate induced peroxidation of rat liver mitochondria. 263 55

When Fe2+ ions are added to rat-liver microsomes, lipid peroxidation begins after a short lag period. Fe2+-dependent peroxidation in the first few minutes of the incubation can be increased by adding Fe3+, ascorbic acid or Pb2+ ions; these stimulations are not additive. By contrast, Pb2+ ions inhibit peroxidation of microsomes in the presence of Fe3+/ascorbate or Fe3+-ADP/NADPH. In liposomes made from ox-brain phospholipids, Fe2+-dependent peroxidation is stimulated slightly by Fe3+, but much more so by ascorbic acid, Al3+ or Pb2+; these stimulations are not additive. Liposomal peroxidation in the presence of Fe3+/ascorbate is inhibited by Pb2+ or Al3+. These results argue against the participation of an Fe2+-Fe3+-O2 complex, or a critical 1:1 ratio of Fe2+ to Fe3+, in the initiation of lipid peroxidation in liposomes and rat-liver microsomes.
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PMID:The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron(II)-iron(III) complex. 270 5

Lipid peroxidation in rat heart and liver microsomes was induced by an NADPH-generating system or by ascorbate in the presence of an ADP-iron complex. Microsomal lipid peroxidation, as measured by malonaldehyde formation, was inhibited by nifedipine over a wide range of concentrations (47 microM to 6 mM). Nifedipine also decreased the oxygen consumption of cardiac and hepatic microsomes in a concentration-dependent manner. These results indicate that nifedipine may perturb microsomal electron transport systems. Nifedipine may have the potential to alter the sensitivity of cardiac and hepatic membranes to peroxidative damage.
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PMID:Inhibition of rat heart and liver microsomal lipid peroxidation by nifedipine. 270 19

The effects of 60 min hypoxia and subsequent reoxygenation for 30 min on enzymatic (NADPH-dependent) and nonenzymatic (Fe2+/ascorbate-induced) lipid peroxidation capacities and on antioxidant levels were studied using Langendorff-perfused rat hearts. The assays were done on the myolayer of the right ventricle (RV) and on the subepi- and subendomyolayers of the left ventricle (epi/endo LV) after normoxic, hypoxic, and reoxygenation phases. The region injured by hypoxia/reoxygenation was located mainly in endo LV, seen as a lesser penetration of the fluorescent dye fluorescein in the myocardium. The electron microscopic findings after reoxygenation revealed swelling of the mitochondria, amorphous mitochondrial structures, and formation of paracrystallines. The myofibrillar structure of the cells was disrupted and the cells showed marked fluid accumulation. Membrane structures were marginated and formed blebs and multilamellar bodies. Ultrastructural changes were most prominent in endo LV, especially after reoxygenation. The increase in leakage of lactate in the perfusate revealed the onset of anaerobic metabolism. Abrupt release of the cytoplasmic enzymes lactate dehydrogenase and creatine kinase at the beginning of the reoxygenation phase suggested cell membrane injury. The capacity for Fe2+/ascorbate-induced lipid peroxidation slightly increased in RV and that for NADPH-dependent, enzymatic lipid peroxidation in endo LV after reoxygenation. Catalase, glutathione peroxidase, and superoxide dismutase activities remained unchanged, whereas glucose-6-phosphate dehydrogenase activity decreased after reoxygenation in RV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic and nonenzymatic lipid peroxidation capacities and antioxidants in hypoxic and reoxygenated rat myocardium. 270 86


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