[Neurotransmitter disturbances in some parts of the rat brain and their correction under chronic and intermittent alcohol intoxication]. / Neiromediatornye narusheniia v nekotorykh otdelakh golovnogo mozga krys i ikh korrektsiia pri khronicheskoi i preryvistoi alkogol'noi intoksikatsii.

The pool of key neuromediators and some neurotransmitter amino acids in cerebellum, hypothalamus and midbrain of rats exposed to chronic and different variants of interrupted alcohol intoxication was investigated. The most pronounced changes were recorded in midbrain. Chronic alcohol intoxication caused an increase in the concentrations of tyrosine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), noradrenaline, tryptophan, serotonin, GABA and aspartate in this part of the rat brain. Interrupted alcohol intoxication with 4 days interval is accompanied by an increase in the content of tyrosine, and noradrenaline. Interrupted alcohol intoxication with 1 day interval leaded to an increase in the concentrations of tyrosine, DOPAC, noradrenalin, tryptophan, GABA, glycine and aspartate. The amino acids composition "Titacin" had a pronounced normalizing effect in the midbrain under interrupted alcohol intoxication with 1 day interval.

[Assessment of the effects of chronic administration of zinc aspartate and zinc sulfate on amino acid metabolism indicators in tissues and the morphology of small intestine in young rats].

Enteral administration (every day, 10 times) of zinc aspartate (33 mg/kg) or zinc sulfate (25 mg/kg) to young rats weighing 50 - 60 g induces an amino acid imbalance in the blood plasma, liver, and myocardium. Zinc sulfate causes much more pronounced changes in the amino acid balance in the liver and myocardium, as compared to that in rats treated with zinc aspartate. One possible mechanism of the above changes can be the effect of zinc salts on nutrient absorption processes and metabolic features of zinc cations in the small intestine.

[Effect of infliximab on amino acid content in blood lymphocytes of alcohol-intoxicated rats].

Dose-dependent effects of monoclonal antibodies to tumor necrosis factor alpha (TNFa) in the form of infliximab preparation have been studied in Wistar rats upon with alcohol intoxication for 10 weeks (Lieber- De Carli liquid diet). It is established that the intraperitoneal administration of infliximab within the last 10 days of alcoholization in doses of 1 mg/kg and 10 mg/kg leads to dose-dependent changes in individual indices of the free amino acids pool and the amino acid balance in blood lymphocytes. Infliximab administered on the background of alcohol intoxication increases the pool of free amino acids and activates their metabolism in rat blood lymphocytes, which is probably due to inactivation of TNFalpha and adaptive changes in the amino acid transport system.

[Effect of tritarg on proteinogenic amino acid spectrum in blood serum and lymphocytes].

Single intragastric injection of tritarg leads to different multidirectional changes in the concentration of free proteinogenic amino acids in the blood serum and lymphocytes isolated from the blood and liver. Changes in the amino acid stock of blood and liver lymphocytes were observed 3 and 24 hours after the drug injection. The changes in concentrations of individual free amino acids are more pronounced in liver lymphocytes than in blood lymphocytes. There is a decrease in the content of proteinogenic amino acids in blood serum, which may reflect the supply of these compounds to cells and is indicative of the stimulation of polypeptide and protein synthesis.

[Toxicological evaluation of chronic exposure to dinil].

Experiments on rats were carried out to study the effect of dinil on the animals on chronic intake of the agent in the quantities exceeding the maximum permissible concentrations by many times. Despite few biochemical changes, there was a certain tension of adaptive processes, which appeared as a change mainly in the integral characteristics of the plasma amino acid pool. The observed changes in the levels of neurotransmitters and neuroactive amino acids in the striatum, midbrain, and hypothalamus are characterized by specific characteristics and may underlie the negative effect of dinil on central nervous system functions. Long-term administration of the agent to the animals did not induce pronounced morphological and biochemical disturbances in the tissues of the liver, heart, and kidneys. Changes in the concentrations of serotonin and neuroactive amine acids in the brain regions might have the greatest consequences to the body. Since the detectable changes in a number of metabolites are likely to be functional in the given period (monthly dinil use), an attempt to correct developing disorders with metabolic therapy agents may be recommended.

[Influence of taurine-zinc sulfate composition on the free amino acid level in blood plasma and the liver].

The intraperitoneal injection of taurine--zinc sulfate composition (400 mg/kg body weight) led to a considerable increase in the plasma taurine levels, activated the hepatic uptake of free amino acids, and modulated the metabolism of sulfur-containing amino acids.

Morphological changes in the liver, thymus, spleen, and small intestine of animals after leucine treatment.

Leucine treatment (100 mg/kg daily for 5 days) leads to activation of the hepatocyte nuclear system and granular endoplasmic reticulum and to a drastic increase in the number of mitochondria, characterized by polymorphism. In the spleen, Malpighian bodies and periarterial lymphoid sheaths are enlarged, lymphocytes infiltrate the periarterial zone, and the mantle zone is enlarged. In the thymus, the width of the cortical matter shrinks, while that of the medulla increases. The content of lymphocytes in the medulla decreases, while that of Hassal's bodies increases. Unambiguous effects of leucine on the small intestinal morphology (mainly on the villous epithelium) were shown. Goblet cells in the villous epithelium were sharply stenosed because of decreased secretory granules in them.

[Using leucine and zinc sulfate for the correction of metabolic disturbances induced by paracetamol].

A mixture of leucine and zinc sulfate (4 : 1; 100 mg/kg body weight) produces a hepatoprotective effect, preventing the ultrastructural injury of hepatic tissue and the disturbance of free amino acid metabolism caused by a toxic dose of paracetamol.

[Glucocorticosteroid status and free amino acid level in blood plasma of rats under increased tolerance to ethanol].

The data are presented on the effects of ethanol treatment (3.5 g/kg of a 25 % solution, singly, daily, intraperitoneally for 1, 4, 7, 10 days) on development of tolerance to ethanol as assessed by changes in ethanol-induced sleep, corticosterone level dynamics and free aminoacis content in rat blood plasma.

[The role of liver antioxidant system in predisposition of rats to hepatotoxic effect of ethanol]. / Rol' antioksidantnoi sistemy pecheni v predraspolozhennosti krys k gepatotoksicheskomu deistviiu étanola.

A new methodological approach capable of revealing factors responsible for the susceptibility of rat liver to ethanol hepatotoxicity has been developed. Using the correlation, dispersion, iteration, multifactor regression, and canonical analyses, a relation was established between the initial state of the liver antioxidant system and the character and degree of the subsequent ethanol-induced damage. In particular, it was found that intact animals with initially low level of reduced glutathione and retinols in the liver, as well as those with enzymopathy of cytosol HDNB-glutathione-8-transferase, are more susceptible to the ethanol liver damage.

[Dynamics of structural changes in rat liver after single dose of gamma-irradiation]. / Dinamika strukturnykh izmenenii v pecheni krys posle odnokratnogo vozdeistviia gamma-izlucheniia.

Histological changes and alterations in biophysical and biochemical parameters in liver of gamma-irradiate rats have been investigated. The gamma-irradiation of the whole body of rats with a single dose of 1 Gy did not cause any impairments of beam structure of rat liver, but resulted in the lymphocytic infiltrations of portal tracts which were not accompanied by formation of spotty areas of necrosis in adjacent areas of lever parenchyma. gamma-Irradiation stimulated proliferation of the hepatocytes and induced time-dependent mitochondrial structure lesions. Post-irradiation changes in cell cytoplasm appeared as disordering in reticulum-endothelial system, among them enlarging and fragmentation of its cisterns, cytoplasmic vacuolization, enhancement of the number of lysosomes and of the lipid inclusion contents. These facts revealed the mobilization of the additional energy resources for recovery of metabolic processes in rat liver. Post-irradiation increase of the level of the hepatocyte membrane lipid peroxidation products preceded liver morphological alterations. The membrane lipid microviscosity decreased in 1 and 3 days after irradiation. As a result of damages of hepatocyte membrane, the activity of the alanin- and asparagin-aminotransferases in blood serum increased 6 hours after. We can conclude that the whole body single gamma-irradiation with a dose of 1 Gy leads to the reversible but significant damages to the rat liver cell membrane structures. These damages might be the reason of radiation-induced liver morphological alterations.

[Regulation of intracellular CoA pool as one of approaches to correction of metabolic disorders]. / Reguliatsiia vnutrikletochnoi struktury fonda KoA kak odin iz podkhodov v korrektsii metabolicheskikh narushenii.

The problems of biosynthesis of coenzyme A, its transport into the mitochondria, and compartmentalization in mammalian cells have been reviewed. Co A pool structure in liver cells and the in myocardium under different pathobiochemical conditionsis discussed. Experimental data which have now been accumulated can be used as a basis for correction of the metabolic disturbances of different etiology.

[The effect of polyamine on the structure of the free amino acid pool in the blood plasma and in the liver of animals with chronic alcoholic intoxication]. / Vliianie poliamina na strukturu fonda svobodnykh aminokislot plazmy krovi i pecheni zhivotnykh s khronicheskoi akkogol'noi intoksikatsiei.

The effect of polyamine on the total content of free amino acids and the structure of the amino acid fund in blood plasma and hepatic tissue was studied in rats with chronic alcoholic intoxication. Rapid utilization of exogenic introduced amino acids and a normalizing effect of the drug on the structure of the amino acid fund were demonstrated. The high concentration of aromatic amino acids in the drug may be among the causes of the increased content of this fraction of amino acids in the tissues studied after administration of the drug.

[Formation of free fatty acid pool in the liver of rats during starvation]. / Formirovanie fonda svobodnykh aminokislot pecheni krys v dinamike golodaniia.

Absolute starvation during 2 days induces increased levels of taurine, phosphoethanolamine, ethanolamine, glycine, serine, threonine and decreased levels of aspartate, lysine, methionine and cystine in the rat liver. The ration of nonessential to essential, and glycogenic to ketogenic amino acids increased on the average by 30%. On day 4 of starvation the level of nonessential glycogenic amino acids is significantly lowered, while the concentration of essential ketogenic amino acids is increased. On day 6 essential ketogenic amino acid pool is more increased. On day 10 the shifts in the amino acid pool in the liver are retained, the reduction of alanine and serine content is most typical. The value of D2-Machalanobis, obtained during lineal discriminant analysis of amino acid pool and space distribution of the signs for the control and starving animals (during 10 days), was lower than that on day 4 and 6 of the experiment. The levels of glycine, serine lysine, leucine, glutamate, alanine and aspartate show the highest information content during such investigation of all the groups of animals.

[Thiamine diphosphate pool and its biosynthesis in the liver in galactosamine hepatitis]. / Pul tiamindifosfata i ego biosintez v pecheni pri galaktozaminovom gepatite.

The hepatitis-like changes were induced in the liver of albino female rats weighing 120-150 g and fed on the appropriate vivarium diet by single parenteral administration of hydrochloride galactosamine in a dose of 0.9 or 1.8 mmol per 1 kg of body weight. The thiamine diphosphate level in the cytosol fraction of the liver decreased 24 h after the preparation administration, the same in blood but with the higher dose used. The activity of pyruvate dehydrogenase, a thiamine diphosphate dependent enzyme, decreased similarly. The cytosol transketolase activity lowered by 38-39%. The coenzyme biosynthesis disturbance due to a fall by 49-58% in the thiamine pyrophosphatase activity is considered to be responsible for hydrochloride galactosamine-induced decrease in the thiamine diphosphate pool. Specificity of the thiamine diphosphate pool disturbance and discoordination of thiamine diphosphate dependent enzymes in the liver are observed under administration of hydrochloride galactosamine.

[Coa biosynthesis and the structure of its reserve in the liver in mice with diabetes (db/db) after administration of pantothenic acid derivatives]. / Biosintez CoA i struktura ego fonda v pecheni myshei s diabetom (db/db) pri vvedenii proizvodnykh pantotenovoi kisloty.

In the liver of genetically diabetic mice (db/db) a rise of CoA and alterations in the structure of its moiety (an increase in CoA/short-chain fatty acyl-CoA and CoA/long-chain fatty acyl-CoA ratios) were found being one of the hyperlipogenesis-providing factors. A rise of the content of CoA in diabetes was caused by the activation of its biosynthesis from vitamin-containing precursors; an increase in the deposition of the latter in panthotenate-protein complexes was also noted. Panthetine and 4'-phosphopanthotenate administration to diabetic animals returned to normal the level of total and free CoA and the ratios of separate components in the structure of coenzyme moiety, and the content of CoA precursors (phosphopantheteine and dephospho-CoA) in the liver.

[Changes in the content and structure of the coenzyme A moiety in the liver of diabetic mice (db/db) administered a regimen of nicotinamide]. / Izmenenie soderzhaniia i struktury fonda koénzima A v pecheni diabeticheskikh myshei (db/db) pri kursovom vvedenii nikotinamida.

Alterations in the content and structure of CoA moiety typical of hyperlipogenesis (a rise in total and free CoA levels, a drop in short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios) were found in the liver of obese mice with non-insulin-dependent diabetes (db/db). The treatment of diabetic mice with nicotinamide, an antilipemic drug, was accompanied by a decrease in total and free CoA levels and a rise in short-chained fatty acyl-CoA content and short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios, probably leading to the inhibition of the enzymes of primary lipogenesis steps. It is suggested that CoA moiety structure is essential as an integral index regulating the rate of fatty acid biosynthesis in diabetes mellitus.

Hepatic CoA, S-acyl-CoA, biosynthetic precursors of the coenzyme and pantothenate-protein complexes in dietary pantothenic acid deficiency.

Weanling rats were fed a pantothenic acid (PA)-free diet for 11 days. Although the animals did not show symptoms of vitamin deficiency, the concentrations of total and free CoA (analyzed with 2-oxoglutarate dehydrogenase), the levels of CoA, dephospho-CoA and 4'-phosphopantetheine (assayed together in the N-acetylation reaction) were decreased. As PA deficiency developed (by days 33-44 of the experiment), the reduction of the content of these metabolites and short-chain acyl-CoA became more pronounced. The level of long-chain acyl-CoA, the ratios of free CoA/total CoA and long-chain acyl-CoA/total CoA remained unchanged. The coenzyme biosynthetic precursors demonstrated the most marked response to the severity of PA deficiency. The relative stability of the hepatocyte CoA pool is interpreted in terms of the cytosol ability to deposit the vitamin in the form of pantothenate-protein complexes.