scholarly journals Effect of oxygen concentration on microsomal oxidation of ethanol and generation of oxygen radicals

1988 ◽  
Vol 251 (3) ◽  
pp. 787-794 ◽  
Author(s):  
S Puntarulo ◽  
A I Cederbaum
Keyword(s):  
Lipid Peroxidation ◽  
Hydroxyl Radical ◽  
Oxygen Radicals ◽  
Liver Microsomes ◽  
Reaction System ◽  
Rat Liver Microsomes ◽  
Biphasic Response ◽  
Microsomal Lipid Peroxidation ◽  
Cytochrome P 450 ◽  
Oxidation Of Ethanol

The iron-catalysed production of hydroxyl radicals, by rat liver microsomes (microsomal fractions), assessed by the oxidation of substrate scavengers and ethanol, displayed a biphasic response to the concentration of O2 (varied from 3 to 70%), reaching a maximal value with 20% O2. The decreased rates of hydroxyl-radical generation at lower O2 concentrations correlates with lower rates of production of H2O2, the precursor of hydroxyl radical, whereas the decreased rates at elevated O2 concentrations correlate with lower rates (relative to 20% O2) of activity of NADPH-cytochrome P-450 reductase, which reduces iron and is responsible for redox cycling of iron by the microsomes. The oxidation of aniline or aminopyrine and the cytochrome P-450/oxygen-radical-independent oxidation of ethanol also displayed a biphasic response to the concentration of O2, reaching a maximum at 20% O2, which correlates with the dithionite-reducible CO-binding spectra of cytochrome P-450. Microsomal lipid peroxidation increased as the concentration of O2 was raised from 3 to 7 to 20% O2, and then began to level off. This different pattern of malondialdehyde generation compared with hydroxyl-radical production probably reflects the lack of a role for hydroxyl radical in microsomal lipid peroxidation. These results point to the complex role for O2 in microsomal generation of oxygen radicals, which is due in part to the critical necessity for maintaining the redox state of autoxidizable components of the reaction system.

scholarly journals The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes

1987 ◽  
Vol 241 (2) ◽  
pp. 561-565 ◽  
Author(s):  
M Fontecave ◽  
D Mansuy ◽  
M Jaouen ◽  
H Pezerat
Keyword(s):  
Lipid Peroxidation ◽  
Rat Liver ◽  
Active Sites ◽  
Oxygen Radicals ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Iron Ions ◽  
Ferrous Ions ◽  
Solid Iron ◽  
Ferric Oxides

Lipid peroxidation in rat liver microsomes induced by asbestos fibres, crocidolite and chrysotile, is greatly increased in the presence of NADPH, leading to malondialdehyde levels comparable with those induced by CCl4, a very strong inducer of lipid peroxidation. This synergic effect only occurs during the first minutes and could be explained by an increase or a regeneration of the ferrous active sites of asbestos by NADPH, which in turn could rapidly be prevented by the adsorption of microsomal proteins on the surface of the fibres. It is not inhibited by superoxide dismutase, catalase and mannitol, indicating that oxygen radicals are not involved in the reaction. It is also not inhibited by desferrioxamine, indicating that it is not due to a release of free iron ions in solution from the fibres. Lipid peroxidation in NADPH-supplemented microsomes is also greatly increased upon addition of magnetite. This could be linked to the presence of ferrous ions in this solid iron oxide, since the ferric oxides haematite and goethite are completely inactive.

scholarly journals Inhibition of microsomal lipid peroxidation by glutathione and glutathione transferases B and AA. Role of endogenous phospholipase A2

1984 ◽  
Vol 220 (1) ◽  
pp. 243-252 ◽  
Author(s):  
K H Tan ◽  
D J Meyer ◽  
J Belin ◽  
B Ketterer
Keyword(s):  
Lipid Peroxidation ◽  
Phospholipase A2 ◽  
Rat Liver ◽  
Inhibitory Activity ◽  
Liver Microsomes ◽  
Supernatant Fraction ◽  
Rat Liver Microsomes ◽  
Microsomal Lipid Peroxidation ◽  
Soluble Supernatant

Lipid peroxidation in vitro in rat liver microsomes (microsomal fractions) initiated by ADP-Fe3+ and NADPH was inhibited by the rat liver soluble supernatant fraction. When this fraction was subjected to frontal-elution chromatography, most, if not all, of its inhibitory activity could be accounted for by the combined effects of two fractions, one containing Se-dependent glutathione (GSH) peroxidase activity and the other the GSH transferases. In the latter fraction, GSH transferases B and AA, but not GSH transferases A and C, possessed inhibitory activity. GSH transferase B replaced the soluble supernatant fraction as an effective inhibitor of lipid peroxidation in vitro. If the microsomes were pretreated with the phospholipase A2 inhibitor p-bromophenacyl bromide, neither the soluble supernatant fraction nor GSH transferase B inhibited lipid peroxidation in vitro. Similarly, if all microsomal enzymes were heat-inactivated and lipid peroxidation was initiated with FeCl3/sodium ascorbate neither the soluble supernatant fraction nor GSH transferase B caused inhibition, but in both cases inhibition could be restored by the addition of porcine pancreatic phospholipase A2 to the incubation. It is concluded that the inhibition of microsomal lipid peroxidation in vitro requires the consecutive action of phospholipase A2, which releases fatty acyl hydroperoxides from peroxidized phospholipids, and GSH peroxidases, which reduce them. The GSH peroxidases involved are the Se-dependent GSH peroxidase and the Se-independent GSH peroxidases GSH transferases B and AA.

scholarly journals The effects of carbon tetrachloride on rat liver microsomes during the first hour of poisoning in vivo, and the modifying actions of promethazine

1969 ◽  
Vol 111 (3) ◽  
pp. 317-324 ◽  
Author(s):  
T. F. Slater ◽  
B. C. Sawyer
Keyword(s):  
Lipid Peroxidation ◽  
Carbon Tetrachloride ◽  
Cytochrome C ◽  
Liver Microsomes ◽  
Inorganic Pyrophosphatase ◽  
Rat Liver Microsomes ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Cytochrome P 450 ◽  
Supernatant Solution

The effects of an oral administration of carbon tetrachloride on various liver microsomal and supernatant components were studied 1hr. and 2hr. after dosing. The modifications of such early changes resulting from a concomitant administration of promethazine together with the carbon tetrachloride were also investigated. The microsomal components studied were: cytochromes P-450 and b5; inorganic pyrophosphatase; NADH– and NADPH–cytochrome c reductases; NADH– and NADPH–neotetrazolium reductases; a lipid-peroxidation system associated with the oxidation of NADPH and stimulated by ADP and Fe2+. NAD– and NADP– DT-diaphorases were measured in the supernatant solution remaining after isolation of liver microsomes, and the distribution of RNA phosphorus between the microsomes and supernatant solution was also determined. Carbon tetrachloride produced a rapid fall in inorganic pyrophosphatase activity, a rather slower decrease in cytochrome P-450 content of the microsomes and small increases in the activities of NADH–cytochrome c reductase and neotetrazolium reductases. The activities of NADPH–cytochrome c reductase, the NADPH–ADP/Fe2+-linked lipid-peroxidation system, DT-diaphorases and the content of cytochrome b5 in the microsomes were unchanged. There was also a loss of RNA phosphorus from the microsomes into the supernatant solution. The RNA phosphorus redistribution, the decrease in inorganic pyrophosphatase and the increases in neotetrazolium reductase activities were at least partially prevented by a concomitant dosing with promethazine. However, the decrease in cytochrome P-450 was not affected by promethazine treatment. These early changes are discussed in terms of the liver necrosis produced by carbon tetrachloride and which is greatly retarded in its onset by the administration of promethazine.

Lipid peroxidation decreases the rotational mobility of cytochrome P-450 in rat liver microsomes

1985 ◽  
Vol 817 (2) ◽  
pp. 217-228 ◽  
Author(s):  
Josef Gut ◽  
Suguru Kawato ◽  
Richard J Cherry ◽  
Kaspar H Winterhalter ◽  
Christoph Richter
Keyword(s):  
Lipid Peroxidation ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Rotational Mobility ◽  
Cytochrome P 450
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