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Biomedical subjects

R Nordmann

Publications and source records attributed to R Nordmann.

134 records · Page 8Linked to original sources
PubMedDate not supplied

Brain membrane disordering related to acute ethanol administration in naive and short-term ethanol-intoxicated rats.

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.

Alcoholic Intoxication↗
PubMedDate not supplied

Hepatic catalase and superoxide dismutases after acute ethanol administration in rats.

The administration of an acute ethanol load (2.3 g/kg, IP) to rats is followed by a decrease of the hepatic activity of cytosolic catalase, a decrease which precedes a reduction in the cytosolic Cu, Zn-superoxide dismutase (SOD) activity. Desferrioxamine, an iron chelator and scavenger of superoxide radicals, administered prior to ethanol, prevents the changes in the cytosolic catalase activity, changes which are unaffected by the administration of allopurinol, an inhibitor of xanthine oxidase. These data favour the hypothesis that acute ethanol results in an overproduction of oxygen free radicals which affects primarily the cytosolic catalase activity and increases hereby susceptibility of Cu, Zn-SOD to these radicals. They suggest also that xanthine oxidase does not play a major role in oxygen radical production in the liver cytosol during acute alcohol intoxication.

Allopurinol↗
PubMedDate not supplied

Inactivation of cerebellar nitric oxide synthase by ethanol in vitro.

The N-methyl-D-aspartate receptor/nitric oxide synthase (NOS)/guanylate cyclase pathway, which plays a crucial role in synaptic plasticity in the brain, is modulated by ethanol. We studied the effect of ethanol in vitro on NOS in rat cerebellum and showed that ethanol (25-200 mM) inactivated NOS in a dose-dependent manner. This inactivation was prevented by the biopterin cofactor tetrahydrobiopterin (BH4) as well as by L-arginine, a NOS substrate, but not by NADPH. These results suggest that ethanol reduces NOS activity by modulating the conformation of the enzyme and thereby its stability, probably by interacting with the binding sites of BH4 and/or of L-arginine. Our data also suggest that inactivation of NOS may contribute to the decrease in the cGMP level, and thus may play a role in the pharmacological actions of ethanol in vivo.

Animals↗
PubMedDate not supplied

Brain membrane sensitivity to ethanol during development of functional tolerance to ethanol in rats.

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.

Animals↗
PubMedDate not supplied

[Alcohol and free radicals: from basic research to clinical prospects].

An oxidative stress occurs in the liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active" fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake.

Alcoholism↗