Search PubMed⌕ Search

Biomedical subjects

F Beaugé

Publications and source records attributed to F Beaugé.

At least 37 records · Page 2Linked to original sources
PubMed1988

Alcohol abuse increases the lipid structural order in human erythrocyte membranes. A steady-state and time-resolved anisotropy study.

The effect of ethanol abuse on the lipid ordering of the human erythrocyte membranes was studied by steady-state and time-resolved fluorescence anisotropy measurements of DPH and its polar analogue TMA-DPH, which probe different membrane regions. Steady-state anisotropy values with DPH as a probe were slightly but significantly increased (+3%) in erythrocyte membranes from alcoholic patients. A resistance to the ethanol fluidizing effect was evidenced in these membranes with DPH and TMA-DPH. No difference in the probe lifetimes was detected between the control and the alcoholic subjects. In the alcoholic patients as compared to the healthy controls, the residual anisotropy for DPH was significantly increased (+7%) corresponding to an increase in the orientational order parameter of 4%; a decrease of the apparent correlation time value was also observed. Nevertheless, no differences between the two erythrocyte populations were observed with TMA-DPH.

Adult↗
PubMed1987

Alterations of erythrocyte membrane organization in alcoholics.

Studies of fluorescence polarization of DPH have shown that erythrocyte membrane "fluidity" and fluidization by ethanol are significantly reduced in alcoholics. By using probes of the polar part of the membrane, ANS and TMA-DPH, in addition to DPH, it was shown in the present study that disturbances also exist in the polar region of the membrane which probably are related to changes in surface glycoconjugates. Furthermore, the acute fluidizing effect of ethanol was correlated with the capacity of the membrane to bind ethanol, which in turn appeared to be linked to the glycans. Chronic ethanol abuse thus causes complex disturbances of membrane organization at different levels of the membrane.

Adult↗
PubMed1987

Membrane properties in behaviorally ethanol-dependent rats.

A way of quantifying alcohol behavioral dependence in rats previously developed was used in the present study to get more insight into the relations between neuronal membrane "fluidity", degree of dependence and membrane "sensitivity" (ethanol partitioning and disordering capacities).

Alcoholism↗
PubMed1986

Membrane fluidity and alcohol dependence.

Rats were chronically intoxicated with alcohol by exposing them to increasing concentrations of ethanol vapor over a 4-week period. They were tested for alcohol consumption in a free choice situation of water and 10% (v/v) alcohol. On the basis of their intakes they were divided into alcohol-dependent and nondependent groups. Synaptosome membrane fluidity evaluated by fluorescence polarization was compared between the two groups and against nonintoxicated controls. The intoxicated animals had a lower membrane fluidity than controls, mainly because of a highly significant increase of rigidity in the alcohol-dependent group. Furthermore, membrane fluidity was found to be correlated with the degree of behavioral dependence (i.e., alcohol intake during the free choice period).

Alcohol Drinking↗
PubMed1985

Alpha 1-adrenergic receptor involvement in norepinephrine-ethanol inhibition of rat brain Na+ -K+ ATPase and in ethanol tolerance.

Norepinephrine (NE) sensitization of rat brain Na+ -K+ ATPase to ethanol (EtOH) inhibition appears to be mediated by alpha 1-adrenoreceptors, since it was reversed by prazosin and WB-4101 (alpha 1-receptor antagonists) in a concentration-dependent manner, but not by yohimbine and piperoxan (alpha 2-receptor antagonists). In addition, clonidine (alpha 2-agonist) and methoxamine (central receptor type uncertain) produced very little sensitization. Chronic EtOH administration to rats for 3 weeks produced tolerance to the hypothermic effect of test doses of EtOH (3 g/kg, i.p.) and a decreased inhibitory effect of NE + EtOH on the enzyme in vitro. This inhibition was still prevented by prazosin and WB-4101. However, the binding of tritiated WB-4101 and prazosin to brain membrane preparations from control and EtOH-tolerant rats revealed that the maximum number of binding sites (Bmax) and the dissociation constant (KD) of alpha 1-adrenoreceptors were decreased after tolerance development. These changes in numbers and binding properties of alpha 1-adrenoreceptors probably account for the decreased NE sensitization of the ATPase to EtOH inhibition in preparations from EtOH-tolerant rats.

Adrenergic alpha-Antagonists↗
PubMed1984

Brain membrane disordering after acute in vivo administration of ethanol, isopropanol or t-butanol in rats.

Brain synaptosomal membranes were prepared from rats sacrificed 18 hr after a single intragastric dose of water or of ethanol (100 mmol/kg), when blood ethanol had fallen almost to zero. Fluorescence polarization of DPH, and (Na+ + K+)ATPase activity, were studied in these membranes in the presence of 0, 0.175, 0.3 or 0.7 M ethanol in vitro. After in vivo ethanol, basal ATPase activity was slightly increased, membrane fluidity was unchanged, but both measures showed increased sensitivity to the effects of ethanol in vitro. Similar results were found after an equivalent in vivo dose of isopropanol, but not of t-butanol. These findings indicate that the sensitization to in vitro effects of ethanol or isopropanol, after in vivo treatment with these alcohols, is probably not dependent principally on their lipid solubilities.

1-Propanol↗
PubMed1984

Temporal correlation of changes in rat brain sialic acid and in inhibition of Na+-K+ ATPase with ethanol tolerance.

Administration of ethanol to rats by gavage, in daily doses increasing gradually from 3 to 6 g/kg, led to progressive development of tolerance to the hypothermic effect of test doses of ethanol (3 g/kg, i.p.), between days 4 and 21 of treatment. Tolerance was decreased by day 3 of withdrawal, and had disappeared by day 7. Basal levels of brain microsomal Na+-K+ ATPase activity increased progressively during tolerance development, and returned to normal by 4 days after ethanol withdrawal. Conversely, inhibition of the ATPase by ethanol alone (0.22-0.66 M), or by 1 microM norepinephrine (NE) combined with much lower concentrations of ethanol (0.0125-0.1 M), decreased progressively during tolerance development, and returned to normal after withdrawal. The best temporal correlation with the degree of tolerance was shown by the magnitude of NE sensitization of the enzyme to ethanol inhibition. The chronic sucrose control treatment resulted in an unexplained increase in the NE sensitization. Since synaptosomal membrane concentration of sialic acid showed a similar time course during ethanol treatment, it is possible that changes in membrane sialic acid contribute to the alteration in NE sensitization by altering NE receptor properties.

Animals↗
PubMed1983

Brain membrane disordering by administration of a single ethanol dose.

There is a bulk of evidence that ethanol exerts an important direct effect on biological membranes, especially in the central nervous system, during chronic administration. Whether membranes are affected after an acute and subacute ethanol administration remains to be demonstrated. Crude synaptic membrane fluidity (checked by fluorescence polarization) together with (Na+ +K+)ATPase activity were therefore examined 18 hours after a single oral ethanol administration (5 g/kg bwt.) to naive rats or to rats previously intubated with ethanol repeatedly during 4 days (increasing the daily dose from 7 to 10 g/kg). The sensitivity of both parameters to different concentrations of ethanol added in vitro (0.175 M-1.400 M) was also determined. Although no changes in the basal intrinsic fluidity were found, (Na+ +K+)ATPase activity increased slightly after administration of ethanol to naive as well as to short-term ethanol intoxicated rats. The fluidizing as well as the ATPase inhibiting effects following the addition of ethanol in vitro were markedly increased 18 hours after ethanol administration to naive rats. Such an hypersensitization seems not to be related to an unspecific stress or to changes in body temperature and was no longer apparent in short-term ethanol intoxicated rats. Disappearance of the acute ethanol induced hypersensitization with further ethanol administration may represent the first stage of tolerance acquisition.

Animals↗
PubMed1983

Brain synaptosomal (Na+ and K+)ATPase activity as an index of tolerance to ethanol.

Variations of brain synaptosomal (Na+ and K+)ATPase activity and development of functional tolerance to ethanol were followed simultaneously throughout a chronic ethanol treatment. Inhibition of the enzyme activity by ethanol added in vitro in the presence of noradrenaline was also assayed. Adult male rats were rendered tolerant to ethanol by daily intragastric administration of doses of 3-6 g of ethanol/kg body wt. As assessed by the hypothermic effect and impairment of motor performance on a tilting plane after injection of a challenge dose of ethanol (3 g/kg body wt. IP), functional tolerance developed slowly, was demonstrable after 2 weeks of treatment and increased for up to 4 weeks. The two tolerance tests gave parallel and positively correlated results. Concurrently with the development of tolerance, the basal activity of brain synaptosomal (Na+ and K+)ATPase increased (7% to 18%) in preparations from ethanol treated animals when compared to those from starch-fed caloric controls, and there was less inhibition of the enzyme by ethanol added in vitro in the presence of noradrenaline. The time course of the appearance of these changes in enzyme activity were positively correlated with that of behavioral tolerance, strengthening a relationship between the phenomena events. The intensity of the noradrenaline-ethanol interaction with the membrane-bound (Na+ and K+)ATPase activity could be an index of the degree of tolerance to ethanol.

Alcoholism↗
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

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↗
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↗
PubMed1979

[Effect of natural amino acids on ethanol oxidation in isolated rat hepatocytes].

The effects of the various naturally occurring amino acids on ethanol oxidation in hepatocytes from starved rats was systematically studied. In order to minimize the non ADH pathways, the ethanol concentration used was 4 mmol/litre, the amino acids being added at the same concentration. In hepatocytes from fasted rats, alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, ornithine and serine increase significantly 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 in these conditions, the results showing no apparent correlation between intracellular glutamate concentration and ethanol oxidation rate, contrarily to previous data. In hepatocytes from fed rats, only alanine, asparagine, cysteine, glycine, hydroxyproline, ornithine and serine increase ethanol oxidation, although to a lesser extent than in cells from starved rats.

Amino Acids↗
PubMed1977

[Comparison of the effect of acetone and isopropanol on lipid metabolism in rats].

Isopropanol and acetone administered to rats in conditions leading to a similar blood acetone level differ markedly in their effects on lipid metabolism. Isopropanol administration determines a fatty liver, which is mainly related to a defect in hepatic lipoprotein synthesis. Acetone administration gives only raise to a slight increase in the liver triacylglycerol level. It does not alter the [1-14C] palmitate, [1-14C] glycerol or [U-14C] leucine incorporation into blood lipoproteins. Acetone does thus not appear to play a preminent role in the isopropanol induced fatty liver which seems to be related mainly to a direct action of the alcohol itself.

1-Propanol↗
PubMed1976

[The possible protective effect of cysteine during acute alcohol intoxication].

In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.

Administration, Oral↗