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H Kappus

Publications and source records attributed to H Kappus.

At least 55 records · Page 3Linked to original sources
PubMed1982

Comparison of methods of assessment of metal-induced lipid peroxidation in isolated rat hepatocytes.

There is some controversy about which method of assessment of lipid peroxidation in isolated hepatocytes is most appropriate. The present study was undertaken primarily to compare measurement of concentrations of thiobarbituric acid (TBA) reacting substances with measurement of ethane concentrations in the gas phase of the incubation flask as indicators of lipid peroxidation. Four metal salts, FeCl2, NaVO3, CdCl2, and MnCl2, were selected as agents that interact with the lipid peroxidation process. Furthermore, reduced glutathione (GSH) concentrations and enzyme leakage were assayed to determine whether there was a consistent pattern of interaction between lipid peroxidation and change in GSH concentrations and enzyme leakage. The effects of the metal ions on the concentration of TBA reactants estimated in the whole cell suspension and on the gaseous ethane concentration were similar. However, the assessment of TBA reactants was a little more sensitive, and ethane concentrations continued to climb with incubation time rather than leveling off as observed for TBA reactants. In general, the results of both assays were in good agreement. No consistent pattern of interaction between lipid peroxidation, GSH, and enzyme leakage was discernible in the results of the present study. It is suggested that perhaps the best approach to an experimental situation where lipid peroxidation is thought to be of central importance is measurement of both parameters, TBA reactants and ethane concentrations.

Animals↗
PubMed1981

Toxic drug effects associated with oxygen metabolism: redox cycling and lipid peroxidation.

Various endogenous and exogenous compounds exert cytotoxic effects via oxygen reduction. In general, these are reduced by intracellular enzymes (reductases of various kinds) in one-electron transfer reactions, before they in turn reduce O2 to O2, the superoxide anion radical. Thus, a cycle is formed of O2 uptake at the expense of cellular reducing equivalents, notably NADPH, generating further active oxygen species (figs 1,2). Structures capable of 'redox cycling' include catechols and other quinone compounds, iron chelates, and aromatic nitro compounds. Several anticancer agents, and also some mutagens, operate on this principle, and their toxic effects may be explained by redox cycling. The particular importance of hypoxic conditions for deleterious O2 effects is given by the concomitant flux through reductive as well as oxidative pathways. Toxic effects include membrane damage resulting from peroxidative reactions of polyunsaturated fatty acids (lipid peroxidation), as well as the attack of reactive oxygen species on proteins (enzymes) and nucleic acids; thus O2 metabolism is linked to carcinogenicity and mutagenicity. Lipid peroxidation is also induced by various halogenated compounds such as carbon tetrachloride. Again, hypoxic conditions are particularly critical because, on the one hand, metabolic activation leading to the free radical is enhanced and, on the other hand, oxygen required for the maintenance of lipid peroxidation is still available. - Powerful antioxidant systems of the cell maintain low steady state concentrations of oxygen metabolites, and toxic effects may, in part, also be explained by the constant drain of reducing equivalents resulting from redox cycling.

Anaerobiosis↗
PubMed1980

Lack of in vivo lipid peroxidation in experimental paraquat poisoning.

Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal dose of paraquat (50 mg/kg) developed signs of pulmonary insufficiency within 3 hours and died within 24 hours. Ethane evolution, a parameter of lipid peroxidation in vivo, was increased over control levels only by 26% after 4 hours. It is concluded that this increase is too small to support the theory that lipid peroxidation is the biochemical mechanism of paraquat toxicity.

Animals↗
PubMed1980

Ethane production of mouse peritoneal macrophages as indication for lipid peroxidation and the effect of heavy metals.

Mouse peritoneal macrophages cultivated for 24 h produced ethane which is a new index for lipid peroxidation reactions, whereas malondialdehyde (MDA), an alternative method, did not increase. This is explained by the metabolism of MDA by macrophages after addition of MDA, whereas the gaseous ethane added remained constant. This indicates that ethane rather than MDA is a reliable parameter for lipid peroxide formation by macrophages. Divalent heavy metal ions were examined for their effect on ethane formation and on cell viability. Whereas the amount of ethane formed by macrophages in presence of CdCl2 and MnCl2 remained fairly constant, PbCl2 and ZnCl2 resulted in decreased ethane production up to 60%. But with all these metals the viability decreased much more and did not correlate with the ethane formation. With some concentrations of FeCl2 an increased ethane formation was observed which was accompanied by decreased viability of the cells. The results are consistent with the view that heavy metals interfere with the oxygen radical reactions of macrophages, and that viability of macrophages is not closely related to these oxidative reactions.

Animals↗
PubMed1980

Oxygen dependence of CCl4-induced lipid peroxidation in vitro and in vivo.

Rat liver microsomes showed an atypical oxygen dependence of carbon tetrachloride (CCL4)-induced malondialdehyde formation with a maximum at ca. 7% O2 and a minimum at ca. 15% O2. Rats treated with CCl4 expired less ethane under high oxygen concentrations and more ethane under low oxygen concentrations. The initiation of CCl4-induced lipid peroxidation in the liver would appear to be influenced by the oxygen concentrations present in the hepatocytes.

Animals↗
PubMed1980

Acute adriamycin treatment of rats does not increase ethane expiration.

Adriamycin (20 and 45 mg/kg) was injected i.p. to rats and the amount of ethane expired, which indicates lipid peroxidation in vivo, was determined. None of the doses applied resulted in significant increased ethane expiration of the animals as measured immediately, on the second or on the third day after treatment. Only with 45 mg adriamycin/kg a small increase of ethane formation could be observed on the second day after treatment. But some rats died during the experimental period. The treatment with 65 mg adriamycin/kg i.p. was lethal within 24 h, although an increased ethane production was not measurable. Our data suggest that lipid peroxidation is probably not occurring during metabolism of adriamycin in the rat, and that it is not responsible for the acute toxicity observed after adriamycin treatment.

Animals↗
PubMed1980

Lysis of erythrocytes as a result of microsomal lipid peroxidation induced by CCl4 or FeCl2.

Rat liver microsomal lipid peroxidation as measured by malondialdehyde formation induced by the NADPH-dependent metabolism of CCl4 led to a concomitant lysis of erythrocytes added to the incubation mixture. The hemolytic process was closely related to the rate of malondialdehyde formation. The time elapsed for initiation and completion of hemolysis and the rate of malondialdehyde formation correlated well with the concentration of CCl4 used. Similar results were obtained during FeCl2-induced microsomal lipid peroxidation and hemolysis. The occurrence of products with hemolytic activity during CCl4-induced microsomal lipid peroxidation is discussed in relation to the hepatotoxicity of CCl4.

Animals↗
PubMed1977

The significance of covalent binding of catechols to proteins in vivo.

When rats were dosed with 14 microgram/kg 3H-isoproterenol, 3H-radioactivity was measurable in the liver until 48 h. This amount was not different in livers of animals which have been pretreated with diethyl maleate. After exhaustive extraction, a significant amount of 3H-radioactivity from isoproterenol could be detected in the proteins of total liver (homogenate), of cytosol and of microsomes. In the cytosol fraction of diethyl maleate pretreated animals twice the amount of isoproterenol-radioactivity was found in the extracted proteins compared to controls. In the microsomal fraction there was no difference between diethyl maleate pretreated and control animals in the amount of radioactivity incorporated into proteins. In all fractions the radioactivity measurable in the extracted proteins declined with a half life time of about 24 h. The in vivo results on covalent binding of isoproterenol are compared to the irreversible protein binding of ethinyloestradiol in vivo. Quantitatively, these in vivo data are compared to the results on irreversible protein binding obtained during incubations of isoproterenol or ethinyloestradiol with rat liver microsomes.

Animals↗