Biomedical subjects
Publications and source records attributed to F Beaugé.
The isopropanol induced fatty liver is prevented in the rat by prior administration of pyrazole. Acetone administration, on the other hand, determines an increase in the hepatic triglyceride level. These results suggest the implications of acetone in the induction of the fatty liver following acute isopropanol administration in the rat.
Isopropanol administration (3 g/kg, p.o.) determines in the rat liver an inhibition of fatty acid oxidation, an enhancement of fatty acid esterification into triacylglycerols as well as an inhibition of lipoprotein secretion which appears to be related to alterations in hepatic phospholipids and which differentiates isopropanol from ethanol induced fatty liver. Disturbances in peripheral lipolysis following isopropanol administration are found only in mature rats and are not necessary to the fatty liver induction.
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Crude synaptic membrane fluidity (checked by fluorescence polarization) together with (Na+ + K+) ATPase activity were examined 18 hours after a single oral ethanol administration (5 g/kg bwt.) to naive rats and to rats previously intubated with ethanol repeatedly during 4 days. The sensibility 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 in both conditions. 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. This hypersensitization was no longer apparent in rats pretreated with ethanol during 4 days. The acute ethanol-induced hypersensitization found in naive rats appears not to be related to an unspecific stress or to changes in body temperature. The disappearance of this hypersensitization in short-term alcohol-intoxicated animals may represent the first stage of tolerance acquisition.
Differentiated membrane alterations correlate with the development of functional tolerance or dependence during chronic alcohol intoxication in humans as well as in animals. In animal studies, a single period of continuous exposure was generally used. In humans, the consumption can be more episodic with heavier weekend drinking. How a heavy but intermittent alcohol exposure over 4 weeks affects the synaptic membrane fluidity and sensitivity was examined in male and female adult rats. No differences were seen between membranes from males and females. Alterations were found in the negative polar membrane region probed by TMA-DPH and the sensitivity to acute ethanol was significantly reduced in the DPH (lipid core) and TMA-DPH probed membrane regions. Tolerance to the hypothermic effect of ethanol has developed and could be correlated with the resistance of the membrane lipid core to ethanol. Intermittent exposures to ethanol, as continuous ones, can result in development of functional and membrane tolerance and in specific alterations in the fluidity of the polar part of the membrane, probably in relation with dependence.
In Wistar rats, which practically avoid ethanol when naive, it is possible to induce a large ethanol intake in a free-choice situation after chronic intoxication by ethanol vapour. In this study, we evaluated the ethanol intake of chronically intoxicated and control rats. The ethanol intake was increased in intoxicated animals but the intensity of the response varied according to individuals without any clear relation to the level of the intoxication. The results clearly showed in intoxicated animals two kinds of responders: alcohol-nonpreferring (27/95) and alcohol-preferring rats (68/95). In the alcohol-preferring rats, ethanol intoxication had induced an alcohol drinking-dependent behaviour; about 75% of the animals of this group drank more than 7 g/kg b.wt. per day and could be considered as behaviourally dependent on alcohol. Furthermore, this group presents most of the criteria of alcoholism that an animal model should ideally satisfy.
(Na+ + K+)ATPase activity and sensitivity to the inhibitory effect of ethanol and noradrenaline in vitro as well as the concentrations of sialic acid, galactose, and hexosamine were determined in erythrocyte membranes in 20 healthy controls and in 20 alcoholic patients within 24 hr of withdrawal. Basal (Na+ + K+)ATPase activity, the sensitivity of the enzyme to inhibition by ethanol and noradrenaline added in vitro, and the concentrations of sialic acid and galactose were significantly reduced in the patients (p less than 0.0005). All of these abnormalities were significantly correlated to each other as well as to the estimated daily quantity of ethanol consumed. After enzymatic removal of terminal sialic acid and terminal and sialic acid-bound beta-galactose, the (Na+ + K+)ATPase differences between the patients and the controls were eliminated. The results showed that the previously reported reduced inhibition of (Na+ + K+)ATPase by ethanol in the presence of noradrenaline in brain membranes in chronically ethanol-fed animals is also found in erythrocyte membranes in alcoholic humans. Abnormal carbohydrate composition of glycolipids and/or glycoproteins of the membrane surface appeared to be related to the (Na+ + K+)ATPase changes, possibly due to interference either with K+ transport or surface electrostatics or, directly or indirectly, with the conformation of (Na+ + K+)ATPase.
Adult male rats were rendered progressively tolerant to ethanol by daily intragastric administration of doses of 3-6 g/kg body weight. Functional tolerance assessed by the hypothermic effect after injection of a challenge dose of ethanol developed slowly and was demonstrable after 2 weeks of treatment. Intrinsic crude synaptosomal membrane fluidity, as assessed by fluorescence polarization of DPH, as well as (Na+ + K+)ATPase activity, did not change significantly during the whole treatment. However, the extra addition of ethanol (0.175-0.700 M) in vitro to the membranes of rats, having received ethanol over a period of at least 2 weeks, fluidized less and inhibited the (Na+ + K+)ATPase activity less than in starch-fed controls. The time-course for the appearance of this membrane hyposensitivity was found to be the same as the time course for the development of functional tolerance to ethanol. The correlation between the degree of functional tolerance and the (Na+ + K+)ATPase sensitivity to ethanol appeared very significant, highlighting the sensitivity of membrane-bound enzymes to detecting adaptive changes in complex biological membranes tolerance.
Erythrocyte membranes from 11 healthy individuals and 11 alcoholic patients, examined within 24 hr of withdrawal, were studied for membrane fluidity as assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene and for the concentrations of sialic acid and galactose in the membrane surface. Basal fluorescence polarization was significantly higher in the alcoholics and the membranes were clearly more resistant to the fluidizing effect of ethanol added in vitro. The concentrations of sialic acid as well as galactose were significantly reduced in the patients. The increased resistance to the fluidizing effect of ethanol added in vitro appeared to be functionally related to reduced concentrations of terminal sialic acid and terminal and sialic acid-bound beta-galactose in the membrane surface. The increased basal rigidity is probably due to concomitant changes in the lipid bilayer of the membrane. The results also showed, for the first time, that similar perturbations of membrane fluidity occur in human alcoholics as have been found previously in chronically ethanol-treated animals.