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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 150-153 
    ISSN: 1432-0738
    Keywords: Bleomycin ; Redox cycling ; Hydroxyl radical ; DNA damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aerobic incubations of bleomycin, FeCl3, DNA, NADPH, and isolated liver microsomal NADPH-cytochrome P-450 reductase resulted in NADPH and oxygen consumption and malondialdehyde formation, indicating that the deoxyribose moiety of DNA was split. All parameters measured depended on the active enzyme, bleomycin and FeCl3. In the absence of oxygen malondialdehyde formation was very low. When bleomycin, FeCl3 and the reductase were incubated with methional ethene (ethylene) was formed, suggesting that during the enzyme-catalyzed redox cycle of bleomycin-Fe(III/II) hydroxyl radicals were formed. Ethene formation also depended on oxygen, NADPH, the enzyme, bleomycin, and FeCl3. During aerobic incubations of bleomycin, FeCl3, NADPH, and isolated liver nuclei oxygen and NADPH were consumed and malondialdehyde was formed. Oxygen and NADPH consumption and malondialdehyde formation depended on bleomycin and FeCl3. In the absence of oxygen malondialdehyde was not formed. These results indicate that nuclear NADPH-cytochrome P-450 reductase redox cycles the bleomycin-Fe(III/II) complex and that the reduced complex activates oxygen, whereby hydroxyl radicals are formed which damage the deoxyribose of nuclear DNA.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 144-149 
    ISSN: 1432-0738
    Keywords: Redox cycling ; Oxygen radicals ; Lipid peroxidation ; DNA damage ; Protein alteration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxic effects of compounds which undergo redox cycling via enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0738
    Keywords: Enzymatic lipid peroxidation ; Phospholipids ; Lysophospholipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Liposomes comprised of liver microsomal phospholipids and radioactive phosphatidylcholine or phosphatidylethanolamine as tracers were incubated with isolated liver microsomal NADPH-cytochrome P-450 reductase, NADPH and ADP-EDTA-chelated iron ions, a system which stimulates peroxidation of unsaturated fatty acids of phospholipids. Phospholipids and their reaction products were extracted and chromatographed on HPLC. Phosphatidylcholine and phosphatidylethanolamine considerably decreased after 30 min incubation, depending on the enzyme and NADPH as measured by UV absorbance and radioactivity. However, neither a lysophospholipid peak nor a lysophospholipid-like peak were detectable. We suggest that lysophospholipid formation during microsomal lipid peroxidation is exclusively due to phospholipase A2 and not due to peroxidative breakdown of the unsaturated fatty acid in the β-position of glycerol.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 52 (1983), S. 135-147 
    ISSN: 1432-0738
    Keywords: Lipid peroxidation ; Ethane ; Pentane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of exhalation of ethane and n-pentane in experimental animals as parameters of lipid peroxidation led to an examination of pharmacokinetics of both compounds in rats. When rats were exposed, in a closed desiccator jar chamber, to a wide range of ethane concentrations, linear elimination pharmacokinetics were observed. n-Pentane, when concentrations higher than 100 ppm were applied, displayed saturation kinetics. These were formally explained by action of two competing metabolizing pathways or enzymes. Application of preexisting models could describe exhalation of both ethane and n-pentane by untreated control rats. Stimulation of lipid peroxidation by ferrous ions or by carbon tetrachloride resulted in dissimilar quantitative behaviours of ethane and n-pentane. Ethane production rates were enhanced after application of both compounds. Because of relatively slow metabolic eliminations this led to markedly elevated concentrations of ethane in the gas phase of the system. Pentane production rates were simultaneously enhanced. However, difficulties in interpretation arise because of rapid metabolic elimination of n-pentane. Compounds that diminish pentane metabolism are shown to evoke higher pentane concentrations in the system than compounds which only enhance the pentane production rate. Determinations of ethane exhalation should provide a more favourable parameter of lipid peroxidation than exhalation of pentane.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 49 (1982), S. 265-273 
    ISSN: 1432-0738
    Keywords: Isolated hepatocytes ; Carbon tetrachloride ; Ferrous ions ; Lipid peroxidation ; Ethane ; n-Pentane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated rat hepatocytes (1×107 cells/ml) were aerobically incubated in Eagle's Minimum Essential Medium which contained 2.0% albumin. As potential parameters of lipid peroxidation ethane and n-pentane formed were measured in samples obtained from the gas phase above the incubation mixture. 15–30 nmol ethane or n-pentane were produced by 107 hepatocytes within 90 min. Carbon tetrachloride (CCl4) or ADP-complexed ferrous ions stimulated ethane and n-pentane formation considerably, depending on the concentrations of the compounds. With CCl4 107 cells formed max 180 nmol ethane and 140 nmol n-pentane within 90 min incubation, whereas with Fe(II) max 130 nmol ethane and 220 nmol n-pentane could be detected. When n-pentane was added to the gas phase above the incubation mixture containing either medium or medium plus hepatocytes its amount decreased by 30% within the first 5 min of incubation. However, afterwards only minor amounts of n-pentane disappeared, even in the presence of hepatocytes. This indicates that n-pentane equilibrates with the cell suspension under the conditions used. Cell viability, as determined by the release of lactate dehydrogenase into the medium and by the uptake of trypan blue by the cells, and the recovery of the cells decreased only in presence of relatively high concentrations of CCl4, or Fe(II) respectively. However, a maximal effect on ethane and n-pentane formation was reached already with lower concentration.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 301-307 
    ISSN: 1432-1041
    Keywords: Rifampicin ; enzyme induction ; oral contraceptives ; 17α-ethinyloestradiol ; oestradiol ; cytochrome P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Liver biopsies were obtained from four patients treated with rifampicin 600 mg for 6–10 days. Hepatic microsomes were incubated with an NADPH-regenerating system and the substrates [2, 4, 6, 7--3H] oestradiol, [6, 7-3H] oestradiol, [2, 4, 6, 7-3H] ethinyloestradiol and [6, 7-3H] ethinyloestradiol. The hydroxylation rates of these steroids at the labelled positions of rings A and B were determined by measuring the transformation of tritium into HTO by the microsomal enzymes. Comparison with previously published data showed that treatment with rifampicin caused a fourfold increase in the rate of hydroxylation of oestradiol and ethinyloestradiol at positions C-2/C-4 of ring A and C-6/C-7 of ring B. The acceleration of oestrogen hydroxylation by rifampicin was paralleled by an increase in microsomal cytochrome P-450, and also by microsomal reduction of rifampicin-quinone, a reactive metabolite of rifampicin. The increased aromatic hydroxylation of oestradiol and ethinyloestradiol leads to enhancement of their irreversible binding to microsomal protein. The data provide an explanation for the diminished efficacy of oestrogens in contraceptive formulations given to patients under treatment with rifampicin.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 66 (1975), S. 1396-1400 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chemistry and Physics of Lipids 45 (1987), S. 105-115 
    ISSN: 0009-3084
    Keywords: chemicals ; drugs ; free radicals ; lipid peroxidation ; reactive oxygen species ; redox cycling
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Free Radical Biology and Medicine 13 (1992), S. 55-74 
    ISSN: 0891-5849
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism 879 (1986), S. 120-125 
    ISSN: 0005-2760
    Keywords: (Rat liver microsome) ; Ethane ; Lipid peroxidation ; Malondialdehyde ; n-Pentane
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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