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Biomedical subjects

R Nordmann

Publications and source records attributed to R Nordmann.

At least 73 records · Page 4Linked to original sources
PubMed1983

Effect of two iron-chelators, desferrioxamine and diethylenetriaminepentaacetic acid, on the development of tolerance to the physical dependence on ethanol in mice.

Physical dependence on ethanol was induced in mice by exposing the animals to increasing concentrations of ethanol vapor for a period of 9 days. The degree of dependence was assessed by subjective scoring of a characteristic behavioral withdrawal syndrome upon cessation of ethanol administration. The daily administration of desferrioxamine (350 mg/kg, i.p.) or of diethylenetriaminepentaacetic acid (200 mg/kg, i.p.) during the ethanol treatment period reduced by 50% the behavioral withdrawal score. On the other hand, an iron-load of 250 mg/kg administered once prior to ethanol treatment and once during ethanol exposure caused a significant increase in the withdrawal score. While the degree of dependence was significantly lowered by the iron chelators, the state of tolerance after chronic ethanol treatment was not altered by these agents. However, the capacity of these ethanol-treated animals to develop rapid functional tolerance at termination of the chronic ethanol exposure was significantly enhanced by desferrioxamine and diethylenetriaminepentaacetic acid. The results are discussed in view of possible role of iron-induced peroxidation of neuronal membrane lipids in the development of tolerance to and dependence on, ethanol.

Animals↗
PubMed1982

Effects of 2-mercaptoacetate in isolated liver mitochondria in vitro. Competitive inhibition of 3-hydroxybutyrate dehydrogenase and depression of the beta-oxidation pathway.

The effects of 2-mercaptoacetate on the respiration rates induced by different substrates were studied in vitro in isolated liver mitochondria. With palmitoyl-L-carnitine or 2-oxoglutarate as the substrate, the ADP-stimulated respiration (State 3) was dose-dependently inhibited by 2-mercaptoacetate. with glutamate or succinate as the substrate. State-3 respiration was only slightly inhibited by 2-mercaptoacetate. In contrast, the oxidation rate of 3-hydroxybutyrate was competitively inhibited by 2-mercaptoacetate in both isolated mitochondria and submitochondrial particles. In uncoupled mitochondria and in mitochondria in which ATP- and GTP-dependent acyl-CoA biosynthesis was inhibited, the inhibitory effect of 2-mercaptoacetate on palmitoyl-L-carnitine oxidation was abolished; under the same conditions, however, inhibition of 3-hydroxybutyrate oxidation by 2-mercaptoacetate still persisted. These results led to the following conclusions: 2-mercaptoacetate itself enters the mitochondrial matrix, inhibits fatty acid oxidation through a mechanism requiring an energy-dependent activation of 2-mercaptoacetate and itself inhibits 3-hydroxybutyrate oxidation through a competitive inhibition of the membrane-bound 3-hydroxybutyrate dehydrogenase. This study also strongly suggests that the compound responsible for the inhibition of fatty acid oxidation is 2-mercaptoacetyl-CoA.

3-Hydroxybutyric Acid↗
PubMed1981

2-Mercaptoacetate administration depresses the beta-oxidation pathway through an inhibition of long-chain acyl-CoA dehydrogenase activity.

To elucidate the mechanisms through which 2-mercaptoacetate administration inhibits fatty acid oxidation in the liver, the respiration rates induced by different substrates were studied polarographically in rat hepatic mitochondria isolated 3 h after 2-mercaptoacetate administration. Palmitoyl-L-carnitine oxidation was almost completely inhibited in either the absence or presence of malonate. Octanoate oxidation was also inhibited, and the intramitochondrial acyl-CoA content was markedly increased. The oxidation rate of pyruvate and 2-oxoglutarate on the one hand and of 3-hydroxybutyrate, succinate and glutamate on the other was either normal or only slightly decreased. In the presence of 2,4-dinitrophenol, the extent of the inhibition of palmitoyl-L-carnitine oxidation was unchanged. All these results are consistent with the hypothesis that the 2-mercaptoacetate inhibition of fatty acid oxidation is due to an inhibition of the beta-oxidation pathway itself. Finally, the mitochondrial defect responsible for this inhibition was shown to be an inhibition of palmitoyl-CoA dehydrogenase activity (EC 1.3.99.3).

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1981

Effect of glucagon on ethanol oxidation in isolated rat liver cells.

Addition of glucagon 5 min after ethanol was found to stimulate the rate of ethanol oxidation in hepatocytes isolated from starved rats. This stimulation is of the same order of magnitude as that mediated by asparagine. The glucagon effect is suppressed by antiproteolytic agents such as insulin or NH4Cl. The stimulating effect of glucagon on ethanol oxidation is probably linked to enhanced proteolysis and an elevated glutamate level in the hepatocytes.

Ammonium Chloride↗
PubMed1981

Liver lipid disposal following t-butanol administration to rats.

Oral administration of a single dose of t-butanol (25 mmol/kg body wt.) to female Wistar rats results in an accumulation of triacylglycerols (TAGs) in the liver. This administration induces an early increase in the rate of palmitate uptake by the liver and a delayed enhancement of the blood free fatty acid (FFA) level. Whereas hepatic lactate/pyruvate ratio and liver fatty acid oxidation appear unimpaired, a highly significant enhancement of palmitate incorporation into liver TAGs occurs after t-butanol administration. This administration impairs the biosynthesis and/or secretion of very low density lipoproteins (VLDLs) as shown by the decrease in both the serum TAG level and the palmitate incorporation into serum TAGs. These data suggest that the metabolic disturbances reported may be related to the stress induced by the administration of t-butanol which is very slowly metabolized, as shown by the sustained blood alcohol level found over a 20-h period. This study also provides evidence that metabolism through the alcohol dehydrogenase (ADH) pathway is not a prerequisite for the ability of an alcohol to induce a fatty liver when administered to rats.

Animals↗
PubMed1980

Evidence against the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase activity in fat cells.

Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.

Adipose Tissue↗
PubMed1980

Comparative study of the effect of amino acids on ethanol oxidation in isolated hepatocytes from starved and fed rats.

The effects of the various naturally occurring amino acids on ethanol oxidation in hepatocytes from 18-hrs starved and fed rats were studied. In order to minimize the non-ADH pathways and to avoid interference with the liver amino acid uptake the ethanol concentration used was 4 mM, the amino acids being added at the same concentration. In hepatocytes from starved rats, asparagine, serine, ornithine, hydroxyproline, histidine, cysteine, alanine, glycine, glutamate, glutamine, aspartate and arginine significantly increase ethanol consumption. The stimulatory effect of glutamine being much less pronounced than the asparagine one and proline being devoid of action, the influence of ammonium chloride addition on ethanol consumption in the presence of these amino acids was studied. Ammonium chloride determines an enhancement of ethanol oxidation, the results showing, contrarily to previous data, no apparent correlation between intracellular glutamate concentration and ethanol oxidation rate but rather a relation with aspartate concentration. In hepatocytes from fed rats alanine, asparagine, cysteine, glycine, hydroxyproline, ornithine and serine still increase ethanol oxidation, although to a lesser extent than in cells from starved rats. It appears that only amino acids which are precursors of either pyruvate or aspartate or glutamate are able to activate the ethanol oxidation. Pyruvate, aspartate and glutamate supply malate-aspartate shuttle components especially in cells from starved rats, pyruvate allowing direct cytosolic reoxidation of NADH in cells from fed rats as well as from starved rats. The relative strengths of the stimulatory effect could be roughly dependent on energy demand for glucose synthesis in starved rats and for urea synthesis in fed rats.

Adenosine Triphosphate↗
PubMed1980

Acute ethanol effects on rat liver tryptophan oxygenase and tyrosine aminotransferase.

In starved rats, ethanol administered acutely enhances tryptophan oxygenase (TO) and tyrosine aminotransferase (TAT) activities. Ethanol also inhibits the early phase of the cortisol-mediated TO and TAT induction. Ethanol administered at the same time as tryptophan does not modify the tryptophan-mediated TO and TAT induction. In cortisol-pretreated rats, ethanol enhances the subsequent TO and TAT induction whereas no additive effects are observed when ethanol is injected together with tryptophan. These results suggest that ethanol mimics the effects of tryptophan on TO and TAT activities. In fed animals, ethanol alone does not result in increased TO and TAT activities, but inhibits their cortisol induction. It increases TO activities when given together with a tryptophan dose which, when given alone, does not enhance these activities. It is suggested that the observed inhibitory effects of ethanol on cortisol-mediated TO and TAT induction in starved and fed animals are related to a defective cortisol transport in the liver cells.

Alcoholic Intoxication↗
PubMed1979

Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.

Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.

1-Propanol↗