[Effects of catalase activators and inhibitors on ethanol pharmacokinetic characteristics and ethanol and aldehyde-metabolizing enzyme activities in the rat liver and brain].

The effects of catalase regulators (aminotriazole, lead acetate, taurine, di-2-ethylhexylphthalate) on the preference for ethanol, its pharmacokinetics, and activities of rat liver and brain ethanol and acetaldehyde-metabolizing enzymes were studied. Lead acetate (100 mg/kg, i.p., 7 days), aminotriazole (1 g/kg, i.p., 7 days), and taurine (650 mg/kg, i.g., 14 days) decreased ethanol consumption under conditions of free choice (10% ethanol water), whereas di-2-ethylhexylphthalate (300 mg/kg, i.g., 7 days) did not exert any effect on this parameter. Taurine, lead acetate and di-2-ethylhexylphthalate significantly activated liver ADH, MEOS and catalase peroxidase activity. Aminotriazole also activated ADH and MEOS, but inhibited liver catalase. The activities of liver and brain A1DH as well as catalase were insignificantly changed by this treatment. The 7-day administration of lead acetate, di-2-ethylhexylphthalate and aminotriazole administrations significantly influenced the ethanol (2 g/kg., i.p.) pharmacokinetic parameters: the area under the pharmacokinetic curve and the elimination half-life time were significantly reduced, whereas the elimination constant and clearance were increased. This unequivocally indicates accelerated ethanol elimination. The 14-day ingestion of taurine insignificantly changed the parameters of ethanol pharmacokinetics in rats.

[Effects of panthenol and carnitine on aldehyde metabolic enzymes in rats with tetrachloromethane-induced liver injury].

Tetrachloromethane (2 g/kg, intragastric) produced a decrease in the activity of NAD- and NADH- dependent aldehyde dehydrogenases with high Km for aldehydes in rat liver. Panthenol and L-carnitine administered separately normalized the activity of aldehyde dehydrogenases, while a combination of the drugs did not produce any significant effect.

[Adrenal glucocorticoid function in rats with various ethanol-induced sleeping time following ethanol administration].

The effect of single and chronic ethanol (Eth) administration (25 % solution, 3.5 g/kg) on functional activity of the hypophyseal-adrenal system in rats with different sensitivity to the hypnotic action of ethanol (short-sleep - SS; non-sleep--NS, long-sleep--LS, intermediate group--IG), was studied. It has been shown that, after a single Eth administration, the concentration of corticosterone (K) in LS rat plasma was 1.5-fold higher than that in the NS animals although it did not differ from the K level in SS and Ig those. After repeated ethanol load, the corticosterone contents in the NS rat blood plasma was 3.5-fold and 4.9-fold lower compared to the control and LS groups, respectively. The data obtained indicate that the SS and LS animals had initially different basal blood plasma glucocorticoid level. The SS animals showed a decreased blood plasma K, whereas the LS ones--an increased one. The features of the glucocorticoid status are suggested to be a factor determining the sensitivity of rats to the ethanol hypnotic effect.

[Effect of acetaldehyde on ethanol- and aldehyde-metabolising systems of the liver and brain of rats]. / Vliianie atsetal'degida na étanol- i al'degidmetaboliziruiushchie sistemy pecheni i mozga krys.

Lately the mechanism of craving for alcohol has been related to the local level of brain acetaldehyde occurring in ethanol consumption and depending on the activities of the brain and liver ethanol and acetaldehyde-metabolizing systems. In this connection, we studied the effect of chronic acetaldehyde intoxication on the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), the microsomal ethanol oxidizing system (MEOS) and liver and brain catalase as well as ethanol and acetaldehyde levels in the blood. The results showed that the chronic acetaldehyde intoxication did not alter significantly the activities of liver ADH, MEOS and catalase as well as liver and brain ALDH. In parallel with this, the systemic acetaldehyde administration led to shortened time of ethanol narcosis and activation of catalase in the cerebellum and left hemisphere, which may indicate involvement of this enzyme into metabolic tolerance development.

[Effect of pyruvate, threonine, and phosphoethanolamine on acetaldehyde metabolism in rats with toxic liver injury]. / Vliianie piruvata, treonina i fosfoétanolamina na obmen éndogennogo atsetal'degida u krys s toksicheskim porazheniem pecheni.

Pyruvate dehydrogenase, threonine aldolase and phosphoethanolamine lyase can produce acetaldehyde during normal metabolism. We studied the effect of loading with the substrates of these enzymes (pyruvate, 500 mg/kg, i.p., threonine 500 mg/kg, i.p., and phosphoethanolamine, 230 mg/kg, i.p.) on the blood concentrations of endogenous acetaldehyde and ethanol and the activities of enzymes producing and oxidizing acetaldehyde in the liver of normal rats and rats with liver injury provoked by chronic carbon tetrachloride (CCl4) treatment (0.2 ml i.p. per rat, 2 times a week during 4 weeks). Blood was collected before the treatment and then 30 min and 1 h following the administration of the substrates to intact and CCl4-treated rats. Endogenous acetaldehyde and ethanol were determined by headspace GC. The CCl4 treatment resulted in decreased liver alcohol dehydrogenase and aldehyde dehydrogenase activities and a significant elevation of liver endogenous ehtanol and a clear tendency to enhance blood acetaldehyde levels. Pyruvate increased blood endogenous acetaldehyde in CCl4-treated animals and endogenous ethanol--in the control group of animals. Threonine elevated endogenous acetaldehyde in normal rats. Phosphoethanolamine increased endogenous ethanol in the intact and CCl4 groups. At the same time, in CCl4-treated rats pyruvate administration increased the liver pyruvate dehydrogenase, threonine decreased threonine aldolase, whereas phosphoethanolamine decreased phosphoethanolamine lyase. Thus, the CCl4 effect on blood endogenous acetaldehyde and ethanol may be mediated through decreased liver ALDH and ADH activities. Liver injury promotes the accumulation of acetaldehyde, derived from physiological sources, including the degration of pyruvate and threonine by decreased acetaldehyde oxidation.

[Metabolic adaptation to alcohol in rats with different preference of ethanol over water]. / Metabolicheskaia adaptatsiia k alkogoliu u krys, razlichaiushchikhsia po predpochteniiu étanola vode.

Recent studies have shown that the phenomenon of ethanol preference by animals and of alcohol consumption by humans may be related to the intensity of its metabolism in the body and depend on the activities of the ethanol and aldehyde metabolizing systems which are potential regulators of the acetaldehyde level in the cell. The special features of adaptative reactions of this system (alcohol dehydrogenase, microsomal ethanol oxidizing system, catalase, aldehyde dehydrogenase) were examined in rats, differing by the preference to water or ethanol (5%, 10%, 15%) under condition of a long contact with alcohol.

[Activity of the enzymes of ethanol and acetaldehyde metabolism in rats with varying initial sensitivity to alcohol]. / Aktivnost' fermentov metabolizma étanola i atsetal'degida u krys s razlichnoi iznachal'noi chuvstvitel'nost'iu k alkogoliu.

The experiments were carried out on male rats with different sensitivity to alcohol. To assess sensitivity to ethanol effects, we have used ethanol-induced sleep time and variations in rectal temperature of alcohol-intoxicated animals. Activity of alcohol dehydrogenase, microsomal ethanol-oxidizing system, catalase and aldehyde dehydrogenase in the liver as well as ethanol and acetaldehyde levels in the blood were determined after alcohol intoxication (3.5 g/kg, i.p., 8 days). The development of alcohol tolerance was accompanied by induction of the microsomal ethanol-oxidizing system in long-sleeping rats and in short-sleeping rats as well as by an increase in ethanol and acetaldehyde levels in the blood.

[Diagnostic effectiveness of determining the activity of certain serum enzymes in alcoholism patients]. / Diagnosticheskaia éffektivnost' opredeleniia aktivnosti nekotorykh syvorotochnykh fermentov u bol'nykh alkogolizmom.

Activities of alcohol, aldehyde dehydrogenases (ADH, A1DH, respectively) and gamma-glutamyl transferase (GGT) were estimated in blood serum of patients with Stages I-III alcoholism (54 men) on admission to the hospital, within 1 hr after ethanol testing (in a dose of 0.4 g/kg of body mass) and during the treatment course. Distinct activation of ADH and GGT and decrease in activity of A1DH were found in the patients as compared with healthy volunteers. Alcohol test did not alter noticeably the enzymatic activity studied. The activity of ADH and GGT was normalized in patients with Stages I-II alcoholism during the treatment course. A1DH exhibited the highest diagnostic efficacy, whose sensitivity and specificity were 92% and 84%, respectively; those for ADH 74% and 86% and for GGT 44% and 90%, respectively. Simultaneous estimation of the activity of the three enzymes improved the sensitivity and efficacy of diagnostic technique and enabled the test to be used as an additional criterion in the diagnosis of alcoholism and in the evaluation of the patients' state and therapeutical efficacy.

[The activities of aldehyde dehydrogenase, GABA-aminotransferase and succinic semialdehyde reductase in the brain of rats with different preferences and tolerances for ethanol]. / Aktivnost' al'degiddegidrogenazy, GAMK-aminotransferazy i reduktazy iantarnogo polual'degida v mozge krys s razlichnym otnosheniem k étanolu i tolerantnost'iu k nemu.

The formation and catabolism of aldehydes were compared in the hemispheres and brain stem of rats preferring ethanol (EP) or water (WP) and of those which were high tolerant (HT) and low tolerant to the hypnotic effect of ethanol. It was shown that aldehyde dehydrogenase was more active in the brain stem of HT-EP rats than that of HT-WR or LT-EP animals, whereas GABA aminotransferase is most active in the hemispheres and brain stem of LT-EP rats. The total activity of succinic semialdehyde reductase was equal in all the groups studied; however kinetic analysis suggest that the enzyme has a higher affinity for the substrate and coenzyme in the brain stem of HT-EP rats. Ethanol administered to HT-EP animals suppressed aldehyde dehydrogenase in the brain stem, unchanged GABA aminotransferase and activates succinic semialdehyde reductase in the two brain structures.

[System of ethanol and acetaldehyde metabolism in the rat liver during the development of ethanol tolerance]. / Sistema obmena étanola i atsetal'degida pecheni krys pri razvitii tolerantnosti k étanolu.

Following daily intraperitoneal injections of ethanol at a dose of 3.5 g/kg rats developed tolerance to its hypnotic action, which was manifested in a drastic decrease of ethanol--induced sleep time and the number of animals sleeping more than 60 min. In the liver, this process was characterized by an elevated alcohol dehydrogenase activity and a decreased aldehyde dehydrogenase one, whereas that of MEOS remained unchanged.

[Endogenous ethanol in the blood and tissues of rats with hypobaric hypoxia]. / Endogennyi étanol krovi i tkanei krys pri gipobaricheskoi gipoksii.

Albino male rats weighing 160-180 g were used to study the effect of short-term hypobaric hypoxia (ascent in an altitude chamber to 2500 m and 5000 m for 1 hr) on endogenous ethanol measured in blood, brain and liver; simultaneously enzymes responsible for ethanol and acetaldehyde metabolism were determined. Endogenous ethanol in blood and tissues was found to be a very sensitive marker of hypoxia which was not correlated with lactate, pyruvate, lipid peroxidation or 11-hydroxycorticosteroids. The latter parameters varied in response to severe hypoxia.

[Biochemical changes in a decrease in the voluntary consumption of alcohol by rats due to lithium chloride]. / Biokhimicheskie izmeneniia pri snizhenii dobrovol'nogo potrebleniia étanola u krys khloristym litiem.

A decrease of alcohol intake by ethanol-preferring rats under free choice conditions after intraperitoneal administration of lithium chloride (35 mg/kg) was accompanied by an activation of aldehyde dehydrogenase in the brain stem, a decrease of dopamine and salsolinol levels in the striatum and normalization of 11-hydroxycorticosteroids contents in the blood and adrenal glands.

[Effect of cyanamide on the level of endogenous ethanol in the liver of normal rats and in hypocorticism]. / Vliianie tsianamida na uroven' éndogennogo étanola v pecheni krys v norme i pri gipokortitsizme.

The rat liver endogenous ethanol level was found to increase under inhibition of aldehyde dehydrogenases by cyanamide. Adrenalectomy results in a decrease of the liver endogenous ethanol content and abolishes cyanamide effect on this index. One of the mechanisms of cyanamide toxic effect may be accumulation of different aldehydes including acetaldehyde.

[Aldehyde dehydrogenase isoenzymes in the rat liver and their role in alcohol preference]. / Izofermenty al'degiddegidrogenazy pecheni i ikh rol' v predpochtenii krysami étanola.

Isoenzymatic spectrum of aldehyde dehydrogenase (AIDH) has been studied in the liver of rats of both sexes. The absence or presence of the fourth isoenzyme of AIDH is apparently an indicator of predisposition of rats to ethanol consumption.

[Characteristics of the hormonal regulation of glycemia in rats with varying alcoholic motivation]. / Nekotorye osobennosti gormonal'noi reguliatsii glikemii u krys s razlicnoi alkogol'noi motivatsiei.

Rats preferring ethanol differ from those preferring water in a lowered blood serum IRI level in the presence of the same level of glycemia. Ethanol preferring animals are characterized by raised function of the adrenal cortex revealed in an elevated II-oxycordicosteroid content in these glands and a lowered cholesterol level. The glucose tolerance test (4 g/kg by intragastric administration) shows a faster depletion of beta-cells of langerhans islets in ethanol preferring animals which is suggestive of a prediabetic state. A different sensitivity of the insular apparatus to glucose is noted in the study group, too. As for glycemia, rats preferring ethanol demonstrate greater resistance to 48-hour starvation as compared to rats preferring water.