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PubMed1975

Effects of zinc deficiency on the oxidation of retinol and ethanol in rats.

The zinc metalloenzyme alcohol dehydrogenase was assayed in subcellular fractions of liver and retina from zinc-deficient and control rats using retinol and ethanol as substrates. When the zinc concentrations of these tissues were reduced because of feeding inadequate dietary zinc, alcohol dehydrogenase was significantly lowered, and the retinol-retinal as well as the ethanol-ethyladehyde conversion was significantly reduced. While in older rats no changes occurred in liver zinc and alcohol dehydrogenase, the retina was more sensitive to the lack of dietary zinc than the liver. Young rats nursed by zinc-deficient dams showed the most severe changes in both tissues. The data suggest that zinc deficiency affects the utilization of vitamin A as well as the catabolism of ethanol.

Alcohol Oxidoreductases↗

PubMed1991

Behavioral and endocrine interactions between thyrotropin-releasing hormone and ethanol in normal human subjects.

Thyrotropin-releasing hormone (TRH) has been shown to antagonize the depressant effects of ethanol in animals, but conflicting findings have been reported in humans. To test whether TRH counteracts any of a variety of ethanol-sensitive behavioral measures in normal human subjects and for an effect of ethanol on TRH-induced thyrotropin (TSH) and prolactin (PRL) response, we administered TRH (500 micrograms) or placebo over 1 min intravenously, 30 min after subjects had ingested 0.8 g/kg of ethanol or a placebo drink. Blood samples for TSH and PRL were drawn prior to and 15 and 30 min after injection. Eight male subjects were studied in a balanced, crossover design with each subject receiving placebo-placebo, TRH-placebo, placebo-ethanol, and TRH-ethanol. Whereas ethanol had significant and expected effects on subjective measures, memory, disinhibition, reaction time and time perception, TRH failed to counteract any ethanol effect, except for a small effect in one memory task. Similarly, no effect of ethanol on TRH-induced TSH or PRL response was found. Though the behavioral findings could be interpreted to indicate that TRH does not alter ethanol sensitive behaviors in humans it will be necessary to utilize higher dosages of TRH and/or TRH analogues before firmly drawing this conclusion.

Adult↗

PubMed2000

Ethanol inhibits development of dendrites and synapses in rat hippocampal pyramidal neuron cultures.

Evidence suggests that some neuropathologic manifestations of Fetal Alcohol Syndrome (FAS) result from the disruption of neuromorphogenesis and synapse formation in the hippocampus. Prior research in this laboratory has shown that ethanol in the medium during the first 24 h in culture increases the number of minor processes (the precursors of axons and dendrites) and accelerates the rate at which axons are formed in low-density cultures of embryonic rat hippocampal neurons. The current study examined the effects of ethanol on the subsequent development of dendrites and synapses in these cultures. Quantitative morphometric analysis utilized double-immunofluorescent staining for MAP2 and synapsin I to visualize dendrites and synaptic specializations, respectively. Six days of ethanol (200, 400 or 600 mg/dl) in the medium, beginning at the time of plating, resulted in decreases in total dendritic length per cell, dendrite number per cell, length of individual dendrites and synapse number per innervated dendrite but had no effect on cell survival. The decrease in synapse number was correlated with dendrite length, suggesting that ethanol's effects on synapse number are secondary to its effects on dendritogenesis. Taken together with our previous findings, these results are the first to demonstrate that ethanol has differential effects on axonal and dendritic growth in a culture model of neurons that are vulnerable to ethanol-induced cytoarchitectural abnormalities during development in vivo.

Alcohol-Induced Disorders, Nervous System↗

PubMed1973

The use of sodium perchlorate in deproteinization during the preparation of nucleic acids.

Sodium perchlorate in high concentrations will remove from solution the detergent sodium dodecyl sulphate and protein complexed with it. This and the failure of proteins to be precipitated by ethanol from solutions containing a high concentration of sodium perchlorate can be utilized as efficient, rapid and simple deproteinization procedures during the preparation of nucleic acids.

Adenine↗

PubMed2001

Influence of temperature and pH on xylitol production from xylose by Debaryomyces hansenii.

The production of xylitol from concentrated synthetic xylose solutions (S(o) = 130-135 g/L) by Debaryomyces hansenii was investigated at different pH and temperature values. At optimum starting pH (pH(o) = 5.5), T = 24 degrees C, and relatively low starting biomass levels (0.5-0.6 g(x)/L), 88% of xylose was utilized for xylitol production, the rest being preferentially fermented to ethanol (10%). Under these conditions, nearly 70% of initial carbon was recovered as xylitol, corresponding to final xylitol concentration of 91.9 g(P)/L, product yield on substrate of 0.81 g(P)/g(S), and maximum volumetric and specific productivities of 1.86 g(P)/L x h and 1.43 g(P)/g(x) x h, respectively. At higher and lower pH(o) values, respiration also became important, consuming up to 32% of xylose, while negligible amounts were utilized for cell growth (0.8-1.8%). The same approach extended to the effect of temperature on the metabolism of this yeast at pH(o) = 5.5 and higher biomass levels (1.4-3.0 g(x)/L) revealed that, at temperatures ranging from 32-37 degrees C, xylose was nearly completely consumed to produce xylitol, reaching a maximum volumetric productivity of 4.67 g(P)/L x h at 35 degrees C. Similarly, both respiration and ethanol fermentation became significant either at higher or at lower temperatures. Finally, to elucidate the kinetic mechanisms of both xylitol production and thermal inactivation of the system, the related thermodynamic parameters were estimated from the experimental data with the Arrhenius model: activation enthalpy and entropy were 57.7 kJ/mol and -0.152 kJ/mol x K for xylitol production and 187.3 kJ/mol and 0.054 kJ/mol x K for thermal inactivation, respectively.

Carbon↗

PubMed2002

Effects of anti-ulcer agents on ethanol-induced gastric mucosal lesions in D-galactosamine-induced hepatitis rats.

Patients with hepatic injury have an increased incidence of gastric ulcers and erosions. In this study, the effect of D-galactosamine(GalN)-induced hepatitis on ethanol-induced gastric mucosal lesions and the protective effect of anti-ulcer agents in rats were examined. Subcutaneous injection of GalN (1 g/kg) remarkably increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities suggesting induction of hepatic injury. Gastric mucosal lesions induced by ethanol were significantly aggravated in GalN-induced hepatitis rats. Orally administered ecabet (CAS 86408-72-2; 20-200 mg/kg) dose dependently inhibited ethanol-induced gastric mucosal lesions in GalN-induced hepatitis rats. Sucralfate (CAS 54182-58-0) tended to inhibit the gastric mucosal lesions at a dose of 200 mg/kg but teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and rebamipide (CAS 90098-04-7) had little effect. All anti-ulcer agents had no effect on the serum ALT and AST activities increased by GalN pretreatment. These results indicate that the gastric mucosa of GalN-induced hepatitis rats is more susceptible to injury induced by luminal irritants such as ethanol. Ecabet potently inhibited gastric mucosal lesions suggesting its clinical utility for the gastric mucosal damage in patients with hepatic injury.

Abietanes↗

PubMed1998

Stimulation of tyrosylprotein sulfotransferase activity by ethanol: role of increased enzyme level.

Tyrosylprotein sulfotransferase (TPST), an enzyme involved in the posttranslational modification of proteins, plays important role in the biological activity and secretion of proteins. Previously we have shown an increased activity of this enzyme in gastric mucosa of alcoholics. In the present study, effect of ethanol on TPST was examined in rat liver and gastric mucosa utilizing enzyme assays and Western blot analyses for TPST levels. Male Sprague-Dawley rats were pair-fed Leiber-DeCarli liquid diets for 10 days and controls received a liquid diet in which dextrose was isocalorically substituted for ethanol. After ethanol feeding, rats were sacrificed and liver and gastric mucosa were processed for Golgi membrane preparation. The TPST activity was measured using poly(Glu6, Ala3, Tyr1) as the sulfate acceptor and PAPS as sulfate donor. There was a threefold increase in TPST activity of gastric mucosa of animals subjected to chronic alcohol feeding. In the liver, the increase in tyrosine sulfating activity was also around threefold. The kinetic studies performed to understand the mechanism involved in ethanol stimulation of TPST activity showed no change in the Km values of the enzyme by ethanol. In control and ethanol-treated animals, the Km for EAY was 0.41-0.53 and 0.43-0.53 microM, and the Km for PAPS was 10-12.5 and 9-17 microM, respectively. The Vmax in ethanol-fed animals was increased by 1.5- to 2-fold. The increase in TPST activity in experimental rats was further tested by analyzing the Western blots by Imaging Densitometer for TPST levels. Analysis of TPST levels also showed over threefold increase in the stomach and liver of ethanol-fed rats. Our results indicate that stimulation of TPST by ethanol involves increased TPST level rather than change in affinity for its substrates.

Animals↗

PubMed2004

Kinetic study on conformational change in a single molecular species, beta3, of beta-conglycinin in an acidic ethanol solution.

The conformational change in a single molecular species, beta3, of beta-conglycinin in an acidic ethanol solution was kinetically studied by the stopped-flow technique, utilizing the intrinsic fluorescence of proteins and the fluorescence of 1-anilinonaphthalene-8-sulfonic acid (ANS) bound to the proteins. The time-course of the intrinsic fluorescence changes clearly showed the rate of conformational change below and above 25% ethanol to be quite different from each other. ANS could bind well to the protein in an ethanol concentration range of 15-25%. However, the rate of conformational change of the protein corresponding to that for ANS binding could not be obtained at less than 25% ethanol, while the rate of conformational change agreed well with that for ANS binding at more than 25% ethanol. In addition, the process showing the greatest and slowest ANS binding was not apparent in the denaturation of beta-conglycinin under the conditions employed. These results lead to the conclusions that the beta-conglycinin structure could be maintained in the mild molten globule-like denaturation state, and that various tertiary structural changes could take place without any significant effect on the high sensitivity of intrinsic fluorescence after the secondary structural changes.

Anilino Naphthalenesulfonates↗

PubMed1999

Production of xylitol by Candida peltata.

The ability of Candida peltata NRRL Y-6888 to ferment xylose to xylitol was evaluated under different fermentation conditions such as pH, temperature, aeration, substrate concentration and in the presence of glucose, arabinose, ethanol, methanol and organic acids. Maximum xylitol yield of 0.56 g g-1 xylose was obtained when the yeast was cultivated at pH 6.0, 28 degrees C and 200 rpm on 50 g L-1 xylose. The yeast produced ethanol (0.41 g g-1 in 40 h) from glucose (50 g L-1) and arabitol (0.55 g g-1 in 87 h) from arabinose (50 g L-1). It preferentially utilized glucose > xylose > arabinose from mixed substrates. Glucose (10 g L-1), ethanol (7.5 g L-1) and acetate (5 g L-1) inhibited xylitol production by 61, 84 and 68%, respectively. Arabinose (10 g L-1) had no inhibitory effect on xylitol production.

Journal Article↗

PubMed1982

Acetaldehyde-induced lipid peroxidation in isolated hepatocytes.

In an effort to evaluate further the concept of ethanol-induced lipid peroxidation, isolated rat hepatocytes obtained via collagenase perfusion were utilized. Hepatocytes were judged to be functionally intact based on measurements of adenosine-5-triphosphate, gluconeogenesis, bromosulphthalein uptake, and trypan blue exclusion. When hepatocytes were incubated with acetaldehyde, a metabolite of ethanol, at 100 mg% and 10 mg%, significant increases in lipid peroxidation resulted as measured by levels of malonaldehyde. Acetaldehyde-induced increases in malonaldehyde were reduced by pre-incubation with antioxidants such as Vitamin E (200 mg%) or glutathione (100 mg%).

Acetaldehyde↗

PubMed1990

Efficient simultaneous saccharification and fermentation of agricultural residues by Saccharomyces cerevisiae and Candida shehatae. The D-xylose fermenting yeast.

Simultaneous Saccharification and Fermentation (SSF) experiments were carried out on agricultural residues using culture filtrate of Sclerotium rolfsii, which produces high levels of cellulases and hemicellulases for the saccharification of rice straw and bagasse, and Candida shehatae--the D-xylose fermenting yeast, and Saccharomyces cerevisiae, both separately and in coculture, for fermenting the released sugars. The coculture system showed efficient utilization of hydrolyzed sugars with 30-38% and 10-13% increase in ethanol production as compared to C. shehatae and S. cerevisiae, respectively, when cultivated separately. SSF simulation studies were carried out using standard sugar mixtures of glucose, xylose, and cellobiose. Both organisms could not use cellobiose, whereas glucose was used preferentially. C. shehatae was capable of utilizing xylose in the presence of glucose.

Candida↗

PubMedDate not supplied

[Conditions for forming ethanol during bioconversion of cellulose-containing raw material].

Several natural associations composed by thermophilic anaerobic bacteria capable of utilizing various cellulose materials at 60 +/- 2 degrees C and pH 6.0-7.0 were isolated from the sludge of Kamchatka geothermal springs. The rate of ethanol production (up to 1.7 g/l per day) and the concentration of ethanol in the medium (up to 1.2%), as well as the fermentation period (10-15 days) were determined under anaerobic conditions in the presence of cellulose, coniferous sawdust, newsprint, or paper pulp as a carbon source. Microorganisms were found that inhibited the production of ethanol. The initial pH value was found to influence both the ethanol production rate and ethanol/acetate ratio. A pH decrease from 7.0 to 5.0 led to 6.7-fold increased the ethanol production and caused a 23.8-fold increase in the ethanol/acetate ratio.

Bacteria↗

PubMed1996

Development and application of a physiologically based pharmacokinetic model for ethanol in the mouse.

The purpose of the present study was to develop a physiologically based pharmacokinetic (PBPK) model in the mouse and to utilize it to evaluate the relative contribution, if any, of gastric alcohol dehydrogenase (ADH) to the bioavailability of ethanol. The PBPK model developed in Swiss Webster male mice accurately simulated blood and brain ethanol concentrations following an intraperitoneal administration of 0.82 and 3.2 g of ethanol/kg body weight. Application of the model illustrated that inclusion of gastric ADH into the model provided a less accurate fit to the experimental data, and therefore gastric ADH did not contribute to the overall disposition of an orally administered ethanol dose of 0.75 g/kg. Furthermore, the model also indicated that changes in percentage cardiac output to the liver had a minimal effect on the blood ethanol concentration (BEC) time curve. The results illustrate the validity of the PBPK model developed for ethanol and demonstrate that in the Swiss Webster male mouse the bioavailability of ethanol is minimally affected, if at all, by metabolism by gastric ADH.

Alcohol Dehydrogenase↗

PubMed1999

Ethanol attenuates lactate production in hypoxic postnatal day 4 rat cerebella.

Ethanol consumption during pregnancy may lead to a low oxygen supply to the brain of the developing fetus. Such a reduction in the oxygen supply will result in changes in intra- and extracellular lactate production, which subsequently may lead to cytoplasmic acidosis, changes in cerebral metabolism, and eventually, cell death. We used a novel application of gas chromatography to measure lactate changes, on a global level, in the cerebellar tissue of postnatal day (PD) 4 and PD 10 rat pups following in vitro exposure of either hypoxia or hypoxia plus ethanol (hypoxia/ethanol). The results showed hypoxia-induced increases in lactate concentrations as a function of treatment time in both PD 4 and PD 10 cerebellar tissue. However, there was a differential response to the additional ethanol treatment between the two age groups assessed, with an attenuation of the time-dependent increase of lactate production following hypoxia treatment in PD 4 cerebellar tissue. The results also indicated that PD 4 cerebellar tissue had increased oxygen utilization when compared with PD 10 tissue exposed to the same conditions. The ethanol-induced reduction in lactate is hypothesized as being due to limitations in glucose transport and utilization under ethanol/hypoxia exposure. It is believed that such limitations in cellular function may initiate a sequence of events that produce at least some of the cerebellar neuronal loss reported in the fetal alcohol literature.

Age Factors↗

PubMed1970

Degradation and utilization of hemicellulose from intact forages by pure cultures of rumen bacteria.

Several pure strains of rumen bacteria have previously been shown to degrade isolated hemicelluloses from a form insoluble in 80% acidified ethanol to a soluble form, regardless of the eventual ability of the organism to utilize the end products as energy sources. This study was undertaken to determine whether similar hemicellulose degradation or utilization, or both, occurs from intact forages. Fermentations by pure cultures were run to completion by using three maturity stages of alfalfa and two maturity stages of bromegrass as individual substrates. Organisms capable of utilizing xylan or isolated hemicelluloses could degrade and utilize intact forage hemicellulose, with the exception of two strains of Bacteroides ruminicola which were unable to degrade or utilize hemicellulose from grass hays. Intact forage hemicelluloses were extensively degraded by three cellulolytic strains that were unable to use the end products; in general, these strains degraded a considerably greater amount of hemicelluloses than the hemicellulolytic organisms. Hemicellulose degradation or utilization, or both, varied markedly with the different species and strains of bacteria, as well as with the type and maturity stage of the forage. Definite synergism was observed when a degrading nonutilizer was combined with either one of two hemicellulolytic strains on the bromegrass substrates. One hemicellulolytic strain, which could not degrade or utilize any of the intact bromegrass hemicellulose alone, almost completely utilized the end products solubilized by the nonutilizer. Similar synergism, although of lesser magnitude, was observed when alfalfa was used as a substrate.

Animal Feed↗

PubMed2002

Conditioning tastant and the acquisition of conditioned taste avoidance to drugs of abuse in DBA/2J mice.

RATIONALE: Conditioned taste aversion (CTA) produced by drugs of abuse such as morphine and cocaine has been interpreted as representing the rewarding actions of these drugs. Evidence for this interpretation is based, in part, on findings in rats indicating saccharin is a more effective conditioning flavor compared to salt (NaCl). However, our studies with ethanol have found salt to be a highly effective conditioning flavor in mice. OBJECTIVES: The present series of studies examined the acquisition of CTA to morphine, ethanol, lithium chloride, and cocaine. Further, saccharin and salt were utilized in each experiment in order to determine effectiveness of each flavor to serve as a conditioning stimulus. METHODS: In four separate experiments, adult male DBA/2J mice were acclimated to a 2 h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1 h access to either 0.15% w/v saccharin or 0.1 M salt followed by 0, 10 or 20 mg/kg morphine (experiment 1), 0, 2, or 4 g/kg ethanol (experiment 2), 0, 1.5 or 3.0 milliequivalents/kg lithium chloride (experiment 3) or 0, 10 or 20 mg/kg cocaine (experiment 4). A fifth flavor access period (trial 5) was not followed by drug exposure. Following trial 5, each subject received 24-h access to the conditioning flavor and water (two-bottle test 1). Control subjects (0 dose groups from each experiment) received a second two-bottle test with 24-h access to both saccharin and salt flavors. RESULTS: Reduced flavor intake and reduced flavor preference was noted in all drug-paired groups in each experiment. However, more rapid development of CTA was seen with the saccharin flavor in morphine- or cocaine-paired groups. In contrast, ethanol-induced CTA appeared more rapidly with the salt flavor. Lithium-induced CTA was modest, and emerged equally with either flavor. CONCLUSIONS: CTA induced by morphine or cocaine in mice occurs in a similar pattern to that seen in rats, and these findings agree with an interpretation based on drug reward. In contrast, ethanol-induced CTA is more likely attributable to aversive effects.

Animals↗

PubMedDate not supplied

Chemistry and pharmacology of an ethanol extract of Bumelia sartorum.

Bumelia sartorum has been mentioned in Brazilian folklore for its reputed use in the treatment of diabetes mellitus and inflammatory disorders. An ethanol extract of root bark elicited a hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, the extract altered glucose tolerance in alloxan-induced diabetic rats, enhanced glucose uptake in skeletal muscle and significantly inhibited glycogenolysis in the liver. These results indicate that the hypoglycemic effect may be similar to chlorpropamide and possibly due to an enhanced secretion of insulin from the islets of Langerhans or an increased utilization of glucose by peripheral tissues. Besides hypoglycemic activity, the ethanol extract also elicited significant anti-inflammatory activity, but did not show any significant effects on blood pressure, respiration or on the various isolated tissue preparations studied. Basic acid has been isolated from the ethanol extract and this component may be responsible for the observed anti-inflammatory activity. However, it is yet to be established whether basic acid is responsible for the observed hypoglycemic activity of the ethanol extract.

Animals↗

PubMed1994

Hypothesis: factors involved in the mechanisms regulating food intake affect alcohol consumption.

In addition to being a pharmacological agent, alcohol (ethanol) can also be considered a food; the body can utilize effectively its calorific contribution. The consumption of alcohol has in many respects the same characteristics as the intake of food. In animal experiments, food intake decreases in relation to the calorific value of the alcohol consumed; in human studies, various results have been obtained from no compensation to full compensation for the contribution from alcohol. If a choice is possible, primarily the carbohydrate part of the diet is decreased for compensation to ethanol intake. Food, in turn, can influence alcohol consumption. There is evidence that it is the carbohydrate content of the diet which influences alcohol drinking. The daily intake of alcohol is equally or even better regulated than intake of carbohydrate, protein, or fat. There is a circadian rhythm of alcohol consumption which resembles the rhythm of food intake. However, the mechanism which regulates alcohol intake does not have a very strong influence on the behaviour of most animals or humans, and its control is often overpowered by outside factors. Nevertheless, it is important to identify the precise mechanism because a better understanding should provide valuable information for use in the search for risk markers and pharmacological treatments for alcoholism.

Alcohol Drinking↗