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S M Zimatkin

Publications and source records attributed to S M Zimatkin.

At least 19 recordsLinked to original sources
PubMed1998

Distribution and kinetics of ethanol metabolism in rat brain.

It was found that the accumulation of acetaldehyde produced from 50 mM ethanol in rat brain homogenates takes place in all major brain regions. The velocity varied between 3.5 to 7.1 nmol/mg of protein/hr. The rate increased in the following order: brain hemispheres, striatum, brainstem, hypothalamus, and cerebellum. Significant regional differences in this process were found: in the initial period of incubation (5 min), acetaldehyde accumulation was maximal in the brain hemispheres; but, in the 30- to 60-min period, it became significantly higher in the cerebellum. Inhibition of this process by the catalase inhibitor, 3-amino-1,2,4-triazole (8 mM), was minimal in the brainstem (27%) and maximal (57%) in the cerebellum, despite nearly complete inhibition of catalase. This would indicate that processes other than catalase activity must contribute to acetaldehyde accumulation.

Acetaldehyde↗
PubMed1997

Alcohol consumption alters monoamine oxidase activities in brain structures: relation to ethanol craving.

BACKGROUND: In spite of numerous biochemical studies the role of brain monoamine oxidase (MAO, EC 1.4, 3.4) in the mechanisms of central alcohol action and the pathogenesis of alcoholism remains unclear. The possible reason of that is the highly heterogeneous distribution of the enzyme in a brain and the different direction of alcohol-induced changes of MAO in various morphological structures. Therefore we used the histochemical approach for examination of the effect of chronic alcohol consumption on MAO A and B activities in definite brain structures: various types of aminergic neurons, glial cells and blood capillaries. METHODS AND RESULTS: For 6 months 180 inbred male rats consumed 15% ethanol as the only source of drinking (mean alcohol consumption was 6 g/kg/day). On the 5-6th months of the experiment animals with maximal (ethanol preferring, EP) or minimal (water preferring, WP) alcohol craving were chosen by testing for free choice between 15% (v/v) ethanol solution and water (3 times, during 2 days, at 2-week intervals). The animals chosen were sacrificed and brain samples were studied by our quantitative histochemical method (23). It was found, that chronic ethanol consumption induced dramatic disturbances in MAO activities in the brain structures strongly depending on the alcohol preference of animals. The total MAO activity in WP rats decreased or remained unchanged, but in EP rats it dramatically increased, especially in neurons of n. raphe pontis and n. raphe dorsalis (1.198 +/- 0.028 and 1.268 +/- 0.018 units as compared to control values 0.594 +/- 0.008 and 0.804 +/- 0.011 units; p < 0.001). MAO A activity in all brain structures containing both forms of the enzyme was increased, especially in EP rats: up to 3 times in neurons of the n. raphe pontis from 0.134 +/- 0.003 units in control to 0.541 +/- 0.013 units; p < 0.001). At the same time in the neurons containing only MAO A activity (n. olivaris superior and n. subcoeruleus) it significantly decreased, especially in WP animals. MAO B activity was reduced in the brain structures of WP rats, but activated or unchanged in EP rats. In all the structures studied the MAO B activity was significantly higher in EP, as compared to WP animals (f.e. in astrocytes: 0.314 +/- 0.012 and 0.200 +/- 0.012 units accordingly, p < 0.001). Despite the significant differences in the degree and direction of the changes in the activity of the MAO forms in rats with different alcohol craving, the calculated share of MAO A in the total MAO activity was regularly increased in all structures studied both in EP and WP animals; the share of MAO B activity accordingly decreased. CONCLUSIONS: Chronic alcohol consumption induces the great disturbances in brain MAO activity and isozyme composition following chronic ethanol consumption, strongly depending of the alcohol craving of the animals. It indicates the involvement of the enzyme in the mechanisms of central alcohol action.

Alcoholism↗
PubMed1997

Alcohol action on liver: dose dependence and morpho-biochemical correlations.

BACKGROUND: Since the duration and the dose of alcohol administration are acknowledged as factors that influence the risk of liver injury, it was interesting to compare the character and degree of liver damage following various doses and methods of alcohol administration. In addition, it was assumed to compare the degree of liver damage histologically and on the activity of marker liver enzymes in blood plasma in the same animals. METHODS AND RESULTS: The several experiments on heterogeneous stock rats with the various daily dose, duration and method of alcohol administration have been carried out. It was found, that the 9-month intake of 15.20% (v/v) ethanol solution as the only source of drinking (the consumption of absolute alcohol was about 4 g/kg/day) did not affect the normal development of animals and did not induce any harmful morphological changes in liver. Moreover, the liver parenchyma looks even better in the context of lesser inflammatory infiltration and vacuolisation of hypatocytes. The activities of the marker liver injury enzymes: alanine and aspartate amino transferases (ALT and AST), alkaline phosphatase (AP) as well as alcohol dehydrogenase (ADH) in blood were also not changed. The intragastric administration 25% (v/v) ethanol (3.5 g/kg twice a day, during 14 days) induced some morphological disturbances in the liver: an extension of blood capillaries and veins in parenchyma and insignificant increasing of the hepatocyte vacuolisation degree (from 0.7 +/- 0.1 points in control to 1.2 +/- 0.2 points in alcohol treated animals). In blood serum, a slight elevation of ADH (from 1.2 +/- 0.2 microM/min/l in control to 1.7 +/- 0.3) and AP (from 236 +/- 19 microM/min/l in control to 278 +/- 25) activities were found. The liquid alcohol diets (mean consumption of absolute alcohol was 14-18 g/kg/day, during a month) induced the more pronounced liver injury: extension of the liver blood vessels, inflammatory infiltration (from 1.1 +/- 0.1 points in control to 2.0 +/- 0.3; P, 0.05) and destruction of hepatocytes (from 0.5 +/- 0.01 points in control to 1.2 +/- 0.1; p < 0.05). Another liquid alcohol diet (mean consumption of absolute alcohol was 20-24 g/kg/day, during a month) induced the expressive hepatocyte vacuolisation (from 0.5 +/- 0.1 points in control to 1.5 +/- 0.2; p < 0.05). In both the experiments, the weaker staining of hepatocyte cytoplasms, basophilia in particular, were found. The activity of blood plasma ADH was insignificantly increased by 47% and 134% and that of AP--by 15% and 38%. The activity of ALT insignificantly increased in the third experiment only and AST remained unchanged. Some correlations among the morphological and biochemical indexes were found in the above experiments: between the degree of hepatocytes vacuolisation and the blood ADH or AP activities (r = 0.62; p < 0.01 and r = 0.54; p < 0.05), accordingly. The oxyphilia intensity correlated with the AST activity (r = 0.64; p < 0.01) and the intensity of hepatocyte basophilia with the ADH activity (r = 0.67; p < 0.01). The negative correlation was also found between the degree of extension of liver blood vessels and the activity of AST (r = -0.57; p < 0.05). CONCLUSIONS: The data obtained confirm the earlier observations concerning the dependence of the degree of liver injury on the dose and manner of alcohol administration as well as great individuality in the liver response to alcohol in heterogeneous stock rats. There are the significant correlations between the some morphological and biochemical markers of alcohol liver injury; among the biochemical markers studied, the ADH activity was the most sensitive.

Animals↗
PubMed1996

Distribution of catalase in rat brain: aminergic neurons as possible targets for ethanol effects.

Ethanol is metabolized at a slow but measurable rate in rodent brain. Recent studies indicate that this process is mediated mainly by catalase. The spatial distribution of this enzyme in different brain structures is poorly known. To explore possible local imbalances between the production and elimination of ethanol-derived acetaldehyde, we investigated the regional and cellular distribution of catalase, histo- and immunohistochemically, using serial cryostat sections from male Wistar rats. Compared to the strong peroxisomal staining seen in liver, brain catalase staining was weak and was not immunologically detected with an anti-sheep bovine catalase antibody. Activity was observed only in microperoxisomes, mainly in perikaryons of aminergic neurons, in the known groups of adrenergic, nonadrenergic and serotonergic neurons of the brain stem. Little peroxisomal staining was seen in other types of brain structures. This result contrasted to that of aldehyde dehydrogenase, which we previously observed to be widely distributed in brain structures, but with low activity in perikaryons of aminergic (especially catecholaminergic) neurons, as compared to cholinergic neurons. Our data indicate that catalase-mediated oxidation of ethanol to acetaldehyde takes place mainly in aminergic neurons, which seem to have a limited capacity for the subsequent removal via aldehyde dehydrogenase. This suggests that locally produced acetaldehyde could mediate CNS effects of ethanol in these structures.

Acetaldehyde↗
PubMed1996

Thiamine deficiency as predisposition to, and consequence of, increased alcohol consumption.

It was found that the activity of the marker thiamine-dependent enzyme, transketolase (TK), was decreased (down to 61-79% of control) in blood, liver and brain of inbred rats following a 6-month consumption of 15% ethanol as their only source of drinking fluid. After ethanol withdrawal, the enzyme activity was gradually restored, but did not reach the control values until 1 month following cessation of alcohol consumption. Moreover, in rats preferring ethanol, the decrease of TK activity was more pronounced than in water-preferring rats. Another experiment showed that thiamine deficiency induced by the thiamine antagonist, oxythiamine (200 mg/kg), led to a prolonged increase of the preferential intake of ethanol solutions in inbred rats. Significantly lower liver TK activities and thiamine pyrophosphate content were found in Finnish AA line rats as opposed to ANA line rats which had been obtained by selective outbreeding for high and low voluntary alcohol intake, respectively. Significantly lower TK activity was also found in the whole brain (89%), cerebellum (79%) and pons-medulla oblongata (87%) of AA rats as compared to ANA animals. Our own findings and the literature data confirm the hypothesis that thiamine deficiency can be both predisposing to and a consequence of, increased alcohol consumption.

Alcoholism↗
PubMed1995

Aldehyde dehydrogenase activities in the brains of rats and mice genetically selected for different sensitivity to alcohol.

Aldehyde dehydrogenase activity in brain has been studied for many years. However, the question of its role in the actions of ethanol in the brain has not been resolved. We have utilized mice and rats selectively bred for sensitivity or resistance to the initial hypnotic effects of ethanol to gain some insight into the possible involvement of brain aldehyde dehydrogenase in the actions of ethanol. We compared the levels of aldehyde dehydrogenase activity in the brains of these selected lines of rodents by histochemical methods. It was found that, although aldehyde dehydrogenase activity was detected in many areas of the brain, only in the cerebellar Purkinje cells was there a difference between sensitive and resistant lines of mice or rats. The resistant lines (Short Sleep mice and Low Alcohol Sensitive rats) had statistically higher levels of aldehyde dehydrogenase than did the sensitive lines (Long Sleep mice and High Alcohol Sensitive rats). Although this does not prove that aldehyde dehydrogenase or aldehydes are involved in the central actions of ethanol, it provides another piece of evidence in this direction.

Alcoholic Intoxication↗
PubMed1994

[Immunoenzyme and immunohistochemical analysis of class III alcohol dehydrogenase from human testis].

An enzyme-linked immunosorbent assay on the basis antialcohol dehydrogenase III (ADH III) monospecific antiserum has been devised. The immunoreactive protein content determined in two samples of human testis autopsy material was 1,288 and 1,047 mg/g of wet weight. ADH III has been revealed in all types of human testicular cells with the maximal content in spermatocytes and spermatogonia.

Alcohol Dehydrogenase↗
PubMed1992

Regional distribution of low-Km mitochondrial aldehyde dehydrogenase in the rat central nervous system.

To clarify the regional capacity of the brain to oxidize biogenic aldehydes and ethanol-derived acetaldehyde, a quantitative immunohistochemical study of the microregional and cellular expression of low Km mitochondrial aldehyde dehydrogenase (mALDH; EC 1.2.1.3) in the rat central nervous system was undertaken, using antiserum raised in rabbit against low-Km aldehyde dehydrogenase purified from rat liver mitochondria. mALDH-specific immunoreactivity (IR) was observed to various extent in the majority of structures in all brain and spinal cord areas. Staining was strong in the extranuclear cytoplasm of neuronal and glial cell bodies but less pronounced in their processes and terminals, the conducting tracts, white matter and neuropile and in blood vessels. Immunostaining density was 2 to 3 times higher in neuronal perikarya as compared with neuropile. mALDH-positive neurons were found in all brain regions, being strongest in the inferior olive and hippocampus stratum pyramidale and weakest in substantia nigra. The percentage of morphologically identifiable ALDH-positive neurons ranged from 40% in the arcuate hypothalamic nucleus to 88% in the cerebellar Purkinje cells. A comparison of the heterogeneous expression of mALDH in various rat CNS regions and cells, as observed in the present study, with the corresponding previously published distributions of the potential acetaldehyde-producing enzymes ADH and cytochrome P450 2E1 indicates major differences, which may help in understanding potential acetaldehyde-mediated CNS effects of ethanol. Knowledge of the regional distribution of high-affinity aldehyde dehydrogenase should also throw light on the neurophysiological role of local regulation of the metabolism of biogenic aldehydes in the brain.

Aldehyde Dehydrogenase↗
PubMed1991

Histochemical study of aldehyde dehydrogenase in the rat CNS.

A quantitative histochemical method was developed to determine aldehyde dehydrogenase (EC 1.2.1.3; ALDH) activity in the CNS. The distribution of ALDH activity in all rat brain and spinal cord regions is described. Among the CNS neuron structures, high enzyme activity was found in receptor and effector neurons, whereas low activity was noted in perikarya of the majority of intermediate neurons, including all aminergic neurons. A positive correlation was demonstrated between the distribution of ALDH activity among rat CNS microregions (our own data) and the density of dopaminergic terminals, dopamine content, and monoamine oxidase activity (literature data) among the same microregions. They may reflect a spatial linkage between ALDH and the predicted sites of natural aldehyde production. Lower enzyme activity was found in phylogenetically younger brain structures. It may explain the differential resistance of CNS structures to ethanol (acetaldehyde). Among the barrier CNS structures, moderate ALDH activity was found in capillaries and surrounding astrocytes and high activity was noted in ependimocytes covering the brain cavities and those of the vascular plexus. This provides realization of the function of ALDH as a brain metabolic barrier for aldehydes.

Acetaldehyde↗
PubMed1989

[Structural changes in the rat cerebral cortex induced by alcohol in combination with aldehyde dehydrogenase inhibitors].

The cerebral parietal cortex in rats subjected to an acute (single) and subacute (for 5 days) ethanol effect in combination with aldehyde dehydrogenase (AldDG) (enzymes classification 1.2.1.3 AldDG) inhibitors--disulfiram and cyanamide--has been investigated histochemically and electron microscopically. The inhibitors mentioned produce an essential decrease of AldDG activity in the cerebral cortex; it remains in some structures even 6 days after their single administration. Against the background of AldDG inhibitors alcohol produces more noticeable structural disorders in the cerebral cortex, they are possibly connected with accumulation of a highly toxic ethanol metabolite-acetaldehyde--in blood and with its easy penetration into the brain. This demonstrates an important role of AldDG in protection of the brain from alcoholic (aldehydic) lesions, as well as a peculiar danger for the brain of ethanol in combination with inhibitors of this enzyme.

Aldehyde Dehydrogenase↗
PubMed1989

[Aldehyde dehydrogenase activity in rat cerebral structures].

By means of the quantitative histochemical method aldehyde dehydrogenase (AldDG; acidic phosphatase 1.2.1.3.) activity has been studied in neuronal structures of all parts of the rat CNS. The greatest activity has been revealed in cytoplasm of receptor (nucleus of the mesencephalic tract trigeminal nerve-1,100 stipulated units) and effector (all motor nuclei of the trunk and spinal cord: 500-800 stipulated units) cerebral neurons. In perikaryons and axons of most of the intercalated neurons AldDG activity is not great (200-300 stipulated units). A positive correlation is found between distribution of AldDG activity among the forebrain structures, on the one hand, and density of dopaminergic terminals, dopamine content and MAO activity of these structures--on the other. In the metencephalon similar correlation is found between AldDG activity and noradrenaline content and density of serotoninergic terminals. A direct dependence is stated of AldDG activity on phylogenic age of the cerebral structures. The data presented demonstrate that AldDG activity is connected with those cerebral structures that are supposed to possess, in the process of common and mediatory metabolism, a high level of natural synthesis of aldehydes.

Aldehyde Dehydrogenase↗
PubMed1988

[Aldehyde dehydrogenase activity in the barrier brain structures].

The histochemical method was used to study the aldehyde dehydrogenase (EC 1.2.1.3.; ALDH) activity in capillaries and glial structures of different regions in the rat central nervous system (CNS). The occurrence of three metabolic barriers for aldehydes on systemic level in the CNS has been shown. They are: the barrier between blood and the nervous tissue (represented by capillary endothelium and surrounding astrocytes ALDH), that between blood and cerebrospinal fluid (ALDH in ependymocytes of vascular plexus), and that between cerebrospinal fluid and nervous tissue (ALDH of ependymocytes covering brain cavities). On the single microregions level a similar barrier is between interstitial fluid and neurons (ALDH of satellite oligodendrocytes).

Aldehyde Dehydrogenase↗
PubMed1988

[Localization of alcohol and aldehyde dehydrogenases in the human spinal cord and brain].

Location of aldehyde dehydrogenase (AldDG) and alcohol dehydrogenase (ADG) has been studied in 38 nuclei of the human brain. Neurons with a high AldDG activity predominate in the nucleus of the descending root of the trigeminal nerve, motor nuclei of the craniocerebral nerves (trigeminal, facial, abducent, blocking, sublingual, supraspinal), motor nuclei of the anterior horns of the spinal cord, lateral vestibular nucleus, posterior nucleus of the vagus nerve, pedunculopontine nucleus, superior salivary nucleus, and in the nucleus of Westphal-Edinger-Jacobovich. Neurons with a moderate AldDG activity predominate in the superior olivary complex, nucleus of the lateral loop, parabrachial (pigmented) mesencephalic nucleus and reticular lateral nucleus. A low enzymatic activity is specific for neurons of the pons proper, inferior vestibular nucleus, trapezoid body of the inferior olivary complex, dentate nucleus of the cerebellum, reticular nucleus of the tegmen of Bekhterev's pons and posterior nucleus of Gudden's suture. A high ADG activity is revealed in piriform neurons of the cerebellar cortex. Functional importance of ADG and AldDG activity in the brain is discussed.

Adult↗
PubMed1982

[Morphometric method in defects of the stomach and intestinal walls].

An ocular micrometer was used to measure a number of parameters of the defect on paraffin slices passing through the center of a wound and gastric or intestinal ulcer: the distance between the edges of the preserved "old" muscular layer and mucous membrane, the width of the non-epithelialized zone of the defect, the length of the layer of newly formed epithelium, the height of the growing connective tissue in the fundus of the defect, etc. Some integral indices may be also calculated from the initial data obtained. The measurement data allow the judgement to be formed on the degree of tissue contraction in the defect area, the magnitude of the growing connective tissue in the defect fundus, the degree of the defect epithelialization and differentiation of the newly formed mucous membrane. The technique suggested is particularly effective during studies into the time course of the defect healing and in the appraisal of the methods for correcting the process.

Animals↗