Chronic Ethanol Intoxication Research Articles

Experimental Model Of Renal Alcoholism And Their Correction Methods

Chronic ethanol intoxication leads to a noticeable increase in the morphometric parameters of parts of the nephron of the kidneys. At 12 months of age during the experiment, the greatest increase in the diameter of the glomerulus (19.8%), the thickness of the Shumlyansky-Bowman capsule (29.1%) and the collecting ducts (25.9%) occurs. The use of polaren syrup slightly reduces the dilated lumen of the tubules, selectively affecting the morphometric parameters of the glomerulus and nephron capsule

The structural rearrangement of testicular arteries in case of chronic ethanol intoxication

Prolonged poisoning of the body with ethanol damages almost all its organs and systems. Structural changes in testicular arteries under the influence of chronic ethanol intoxication have not been fully studied. Purpose - to analyze the morphometric parameters of the small caliber arteries of the right and left testicles of rats in case of chronic ethanol intoxication. Materials and methods. 62 laboratory sexually mature male rats was performed. The animals were divided into two groups. The Group 1 (control) included 30 rats, the Group 2 (experimental) - 32 animals. The experimental rats, which were conducted to the experiment, were injected intragastrically with a 30% ethanol solution at the rate of 2 ml per 100 g of body weight for 28 days once a day. Animals were euthanized by heart bleeding under thiopental anesthesia. Histological micro-sections were made from the left and right testicles. Morphometrically, the outer and inner diameters of the arteries, media thickness, adventitia, Vogenvoort and Kernogan indices, the height of endotheliocytes, the diameter of their nuclei, the nuclear-cytoplasmic ratio in these cells, and the relative volume of damaged endotheliocytes were determined morphometrically in small-caliber arteries. Statistical processing of digital data was carried out using Excel (Microsoft, USA) and STATISTICA 6.0 (Statsoft, USA) software. Results. It was established that in case of simulated experimental conditions of chronic ethanol intoxication, the investigated morphometric parameters of the arteries of the left and right testicles changed significantly. In case of chronic intoxication with ethanol in rats, pronounced structural rearrangement of testicular vessels, mainly small arteries, characterized by thickening of the blood vessel’s wall, narrowing of vessels’ lumen, rearrangement of endothelial cells, and an increase in the relative volume of the damaged cells of intima, is established, and is dominant in the left testis. Conclusions. In case of chronic intoxication with ethanol the structural changes in testicular tissues are dominant in the left testis. Pronounced remodeling of small caliber testicular arteries causes endothelial dysfunction, deterioration of blood supply to the testicles, hypoxia, dystrophic and necrobiotic tissue changes, infiltrative and sclerotic processes, which are the pathomorphological basis of male infertility. When carrying out experiments with laboratory animals, all bioethical norms and recommendations were observed. No conflict of interests was declared by the authors.

Central Effects of Peripherically Introduced Immune Cells Modulated by an Original Anticonvulsant in Experimental Alcoholism

Violation of neuroimmune regulatory interrelation, caused, in particular, by a change in the immune cell’s functional phenotype due to chronic ethanol intoxication, is an essential link in the pathogenesis of alcoholism. The unidirectional influence of most psychoactive drugs on the cells of the nervous and immune systems allows to consider immune cells as model objects for influencing intersystem functional interrelation. Based upon our own priority data on the presence of immunomodulatory properties in chronic alcohol intoxication at the original anticonvulsant acting on the molecular targets of ethanol influence in the central nervous system and the immune system, the aim of the present study was to evaluate the central effects of peripherally injected lymphocytes with in vitro modulated functional activity by a synthetic ligand of the GABAA-receptor complex meta-chlorobenzhydrylurea in long-term alcoholized animals. It was shown that transplantation of lymphocytes pre-cultivated with the anticonvulsant in syngeneic long-term alcoholic recipients achieves a decrease in alcohol motivation and stimulation of behavioral activity in the “open field” test. Editing of behavioral patterns characteristic for chronic alcohol intoxication was recorded against the background of a decrease in pathogenetically significant brain structures of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ and an increase in the anti-inflammatory cytokine IL-10, as well as an increase in the level of BDNF in the hippocampus, which allows us to consider a decrease in neuroinflammation and stimulation neuroplasticity as possible mechanisms for editing the behavior of recipients. Visualization of functionally active lymphocytes pre-cultured with meta-chlorobenzydrylurea in the brain’s parenchyma of long-term alcoholized recipients also suggests a direct effect of injected lymphocytes on CNS cells. Thus, immune cells modulated in vitro with meta-chlorobenzydrylurea by relatively independent mechanisms have positive psychoneuromodulating effects in chronic ethanol intoxication, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.

Significance of the liver arginase activity and nitrogen monoxide in the detoxification processes and development of oxidative stress in rats under alcoholic intoxication of different severity

Modern medicine faces the problem of the steady growth of alcoholic pathology. And as you know, morbidity and mortality with regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, the liver. To date, a sufficient number of facts have accumulated indicating the importance of liver arginase and nitrogen monoxide (NO) in vital processes in health and disease.The aim of the study was to elucidate the significance of liver arginase activity and nitrogen monoxide in the detoxification processes and the development of oxidative stress in rats with chronic ethanol intoxication of different severity.In experiments on rats using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase and nitrogen monoxide participate in changes in liver detoxification function and the development of oxidative stress induced by chronic ethanol intoxication. The direction and severity of changes in arginase activity and liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30 % aqueous solution of ethanol (3.5 g 92 % ethanol per kg of body weight) in animals under conditions of development of oxidative stress inhibited the activity of liver arginase and detoxification function but and the introduction of a 10 % aqueous solution of ethanol (1.0 g 92 % ethanol per kg of body weight) within 2 months leads to an increase in the activity of liver arginase and detoxification processes. The action in the body of the NO-synthase blocker methyl ester NG-nitro-L-arginine weakens, and the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and lipid peroxidation in the liver during chronic alcohol intoxication caused by intragastric the introduction of ethanol at a dose of 3.5 g/kg for 60 days.

Comprehensive analysis of transcriptomics and metabolomics to understand chronic ethanol induced murine cardiotoxicity.

Alcohol abuse has attracted public attention and long-term alcohol exposure can lead to alcohol-featured non-ischemic dilated cardiomyopathy. However, the precise underlying mechanisms of alcoholic cardiomyopathy remain to be elucidated. This study aimed to comprehensively characterize alcohol abuse-mediated effects on downstream metabolites and genes transcription using a multi-omics strategy. We established chronic ethanol intoxication model in adult male C57BL/6 mice through 8weeks of 95% alcohol vapor administration and performed metabolomics analysis, mRNA-seq and microRNA-seq analysis with myocardial tissues. Firstly, ethanol markedly induced ejection fraction reductions, cardiomyocyte hypertrophy, and myocardial fibrosis in mice with myocardial oxidative injury. In addition, the omics analysis identified a total of 166 differentially expressed metabolites (DEMs), 241 differentially expressed genes (DEGs) and 19 differentially expressed microRNAs (DEmiRNAs), respectively. The results highlighted that alcohol abuse mainly interfered with endogenous lipids, amino acids and nucleotides production and the relevant genes transcription in mice hearts. Based on KEGG database, the affected signaling pathways are primarily mapped to the antigen processing and presentation, regulation of actin cytoskeleton, AMPK signaling pathway, tyrosine metabolism and PPAR signaling pathway, etc. Furthermore, 9 hub genes related to oxidative stress from DEGs were selected based on function annotation, and potential alcoholic cardiotoxic oxidative stress biomarkers were determined through establishing PPI network and DEmiRNAs-DEGs cross-talk. Altogether, our data strongly supported the conclusion that ethanol abuse characteristically affected amino acid and energy metabolism, nucleotide metabolism and especially lipids metabolism in mice hearts, and underlined the values of lipids signaling and oxidative stress in the treatment strategies.

Gastrointestinal Injuries Following the Acute and Chronic Alcohol Abuse: An Update

The deleterious health effects of ethanol abuse are widely known and a diversity of medical conditions appear with excessive consumption. Acute and chronic abuse have different clinical characteristics, although severe intoxications are rare among alcoholics of a long career, where the systemic complications will dominate the symptomatology. While the medical focus acutely will mostly stay on the nervous and circulatory effects, gastrointestinal complications that will come up chronically (liver, pancreas, bowel dysfunction) need proper consideration. Ethanol will affect gastrointestinal functionality through a triple action, directly on the epithelial cell and the secretory activity, by altering the motility and in the long-term scope, through promoting carcinogenesis. Medical teams dealing with acute and chronic ethanol intoxication or abuse must be aware of the multiple effects it shows, and perform a prompt diagnosis as well as appropriate intervention.

Alterations in The Functional and Structural Properties of Erythrocytes Due to Alcohol Intoxication; Correction of Disorders

Alcohol abuse is among the leading reasons for disability and accounts for at least 5% of the global health burden. This study aims to define changes in the functional and structural properties of erythrocytes in chronic ethanol intoxication and to design methods for correction of the identified disorders. The experiments has been conducted on 93 healthy sexually mature and newborn Wistar rats. Acute and chronic alcohol intoxication has been designed by forced intragastric administration of 20% ethanol solution at a dose of 3 ml/kg (2.92 g/kg) on a daily basis for 5, 30 and 60 days. From the newborn animals we obtained allogeneic hepatocytes and their cultural fluid, from which proteins were isolated. The proteins of allogeneic hepatocyte and the combined administration of immunomodulatory, hepatoprotective and antioxidant agents were used to correct disorders in chronic intoxication. The membranes of circulating erythrocytes were obtained by the method of Dodge; electrophoretic separation of membrane proteins was carried out according to the method of Laemli. The lipid content in the erythrocyte membrane was determined by liquid thin-layer chromatography. It has been elucidated that in presence of chronic alcohol intoxication there is a change in the content of the membrane proteins in circulating erythrocytes, which are responsible for flexibility and shaping, intrinsic cellular metabolism, stabilization and structure formation, and a disruption in the lipids representativeness and ratio that form the basis for the lipid framework of the plasmalemma and play the major role in arrangement of protein macromolecules and the normal metabolism of red blood cells as well. When analyzing the corrective activity of the proteins of allogeneic hepatocytes and the combination Glutoxim + Mexidol + Heptral, we have established their high efficiency towards the disorders in the functional and structural properties of circulating erythrocytes caused by chronic alcohol intoxication.

Derivatives of 3-Hydroxypyridine in The Correction of Disorders in The Structural and Functional Properties of Erythrocytes in Experimental Acute Destructive Pancreatitis Due to Chronic Ethanol Intoxication

At present, acute pancreatitis only in some areas is a rather well-studied disease of the abdominal organs, however, the destructive forms of this disease have various developmental patterns, complications and, often unfavorable outcomes. The aim of the research is to establish the possibilities to correct the disorders in the functional and structural features of erythrocytes by 3-hydroxypyridine derivatives in experimental acute destructive pancreatitis due to chronic ethanol intoxication. In experimental acute destructive pancreatitis due to a 60-day ethanol intoxication there was a decrease in the content of proteins (a - ? ß -spectrin, ankyrin, anion transport protein, actin, gyceraldehyde-3-phosphate dehydrogenase, glutation-S transferase) and lipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, glycerophospholipids, sphingomyelin, phospholipids, triacylglycerol, sum of mono- and diacylglycerol), an elevated level of band 4.1 and 4.5 proteins, pallidin, dematin, tropomyosin and lipids (lysophosphatidylcholine, cholesterol, it’s esters, non-esterified fatty acids), a disorder in intrinsic cellular metabolism of erythrocytes (an increased concentration of lipid peroxidation products, a decreased activity of catalase, superoxide dismutase, degree of stable metabolites of nitrogen oxide and sorption indicators of membrane) in the erythrocyte membrane. The study has revealed that the greatest efficiency in correction of disorders in the functional and structural feutures of erythrocytes from among the derivatives of 3-hydroxypyridine has a compound ß - hydroxynicotinoylhydrazon 2-methyl-3-hydroxy-4-formyl-5-oxymethylpyrydine dihydrochloride, and the least one - 2-ethyl-6- methyl-3-hydroxypyrydine malate (etoxydol), the administration of 2-ethyl-6-methyl-3-hydroxypyrydine succinate (mexidol) has shown an intermediate result.

Proteome-wide analysis of the hippocampus in adolescent male mice with learning and memory impairment caused by chronic ethanol exposure

Alcohol consumption may cause various impairments in the brain. The hippocampus is particularly vulnerable to alcohol exposure, which may cause learning and memory deficits. Recently, proteomics analysis has become a popular approach to explore the pathogenesis of various diseases. The present study was conducted to investigate protein expression alteration in the hippocampus and to identify the molecular mechanisms underlying ethanol-induced learning and memory impairments. Mouse models of chronic ethanol intoxication were established by intragastrical administration for 28 consecutive days, and hippocampal neuronal damage was assessed by Nissl staining. Recognition memory was evaluated by Novel object recognition and Morris water maze tests, and hippocampus tissues were collected for label-free quantitative proteomics and analyzed using bioinformatics methods. Our study showed that chronic ethanol exposure prompted marked changes in protein expression in the hippocampus. We identified 32 differentially expressed proteins, of which 21 were upregulated and 11 downregulated. Gene Ontology analysis suggested that the identified differentially proteins were mainly involved in cytoskeleton and signal transduction mechanisms. Further verification using Western blotting and real-time quantitative PCR revealed that the hippocampal CTSL (cathepsin L), and PVALB (Parvalbumin) showed strongest expression changes, the latter being specifically expressed in GABAergic interneurons. These two proteins might serve as candidate protein biomarkers, providing new prospects for the diagnosis and treatment of ethanol-induced learning and memory disorders.

Efficiency of the original flavonoids composition based on Curcumin in chronic alcohol intoxication

IntroductionMultiple tissue and organ damage induced by ethanol toxic effects requires prescription of a wide range of drugs that have a positive symptomatic effect, while simultaneously increasing the toxic load on the body, which necessitates the search for new approaches to the therapy of alcoholism, possibly with the use of parapharmaceuticals.ObjectivesThe anti-inflammatory, antioxidant and neuroprotective properties of curcuminoids, as well as their ability to influence the epigenetic mechanisms of gene expression regulation, can provide a positive therapeutic effect in alcoholism by influencing the pathogenetic mechanisms of this pathology, which determines the relevance and prospects of studying their effects during chronic ethanol intoxication.Methods(CBAxC57Bl/6) F1 male mice with 6-month 10% ethanol exposure were undergoing administration of original composition of flavonoids based on Curcumin for 40 days. Animal’s alcohol consumption, behavior and immune parameters were estimated.Results As a result of flavonoids original composition administration, correction of the changes in the nervous system functional activity, caused by the chronic toxic effect of ethanol has been achieved (decrease in alcoholic motivation, exploratory behavior stimulation, modulation of the cytokines level in brain, indicating a neuroinflammation decrease). We also registered the immune system functional activity modulation (stimulation of immune response and lymphocytes proliferative activity) in mice with alcohol dependence.ConclusionsThe original composition of flavonoids against the background of long-term alcohol consumption has a positive psychoneuroimmunomodulatory effect, which serves as an experimental substantiation of the prospects of using the composition as an adjuvant in the treatment of chronic alcoholism.DisclosureNo significant relationships.

Significance of the activity of liver arginase and Kupffer cells in the detoxification processes and the thyroid status formation in rats under alcoholic intoxication of different severity

Modern medicine faces the problem of a steady growth of alcoholic pathology. As you know, morbidity and mortality with a regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, on the liver. To date, a sufficient number of facts are accumulated, indicating the importance of liver arginase and Kupffer cells in vital processes in health and disease. The aim of the study was to elucidate the significance of the activity of liver arginase and Kupffer cells in the detoxification processes and the thyroid status formation in rats with chronic ethanol intoxication of different severity. In rat experiments using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase and Kupffer cells participate in changes in the liver detoxification function and the thyroid status formation induced by chronic ethanol intoxication. The activity of liver arginase and Kupffer cells determines the severity of detoxification processes and the thyroid status formation in chronic alcohol intoxication. The direction and severity of changes in the arginase activity and the liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30 % aqueous solution of ethanol (3.5 g 92 % ethanol per kg of body weight) in animals inhibited the activity of liver arginase and the detoxification function, but the introduction of a 10 % aqueous solution of ethanol (1.0 g 92 % ethanol per kg of body weight) within 2 months leads to an increase in the activity of liver arginase and detoxification processes. Kupffer cells depression by GdCl3 as the action in the body of the NO-synthase inhibitor methyl ester NG-nitro-L-arginine weakens and the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and triiodothyronine level in plasma during chronic alcohol intoxication caused by intragastric introduction of ethanol at a dose of 3.5 g/kg for 60 days.

Influence of Chronic Ethanol Intoxication on Hemodynamics in Testicles and Spermatogenesis in Middle-Aged Males

Diseases of testicles are an important social problem because according to WHO data, the male factor is about 45% in the structure of sterile marriage. Among many pathogenic factors distorting spermatogenic and endocrine function of testicles, acute and chronic circulatory disorders in them play a great role. Recent studies showed that one of the causes of male infertility is chronic ethanol intoxication causing distorted hemomicrocirculation in testicles, so determining the character of cytologic changes in them in these circumstances remains relevant.
 Objects and methods. In the study, we used 14 histological micropreparations from testicular biopsy specimens from middle-aged infertile males (22-35 years) with chronic alcoholism in anamnesis,. In some biopsy specimens, ultrastructural changes in testicles were studied under the electronic microscope, testicular hemodynamics in infertile males was examined with ultrasound.
 Results. In middle-aged infertile males with chronic alcoholism, the volume of testicles decreases compared to normal. The arterial blood flow rate in them decreases significantly. The diameter of tortuous looped seminiferous tubules decreases compared to normal. Their membrane is thickened; the layers of spermatogenic epithelial cells are reduced. The volume of interstitial endocrinocytes decreases compared to normal. Testosterone level in blood decreases too.
 Ultrastructural changes in testicles are manifested with irregular thickness and curving of spermatogenic epithelial basal membrane, vacuolization of myoid cellular, supporting epitheliocytes, and interstitial endocrinocyte cytoplasm with reduced mitochondrial cristae and tubules in the endoplasmic reticulum. In ejaculate of infertile males, sperm concentration decreases to (30.65±1.70) million/ml compared to (75.80±4.20) million/ml, the number of pathologic forms of spermatozoids increases twice, the number of spermatozoids with progressive movement decreases.

ОБ УЧАСТИИ АРГИНАЗЫ ПЕЧЕНИ В ПРОЦЕССАХ ДЕТОКСИКАЦИИ И РАЗВИТИЯ ОКСИДАТИВНОГО СТРЕССА У КРЫС В УСЛОВИЯХ АЛКОГОЛЬНОЙ ИНТОКСИКАЦИИ РАЗЛИЧНОЙ ТЯЖЕСТИ

Modern medicine faces the problem of the steady growth of alcoholic pathology. And as you know, morbidity and mortality with regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, the liver. To date, a sufficient number of facts have accumulated indicating the importance of liver arginase in vital processes in health and disease. The aim of the study was to elucidate the significance of liver arginase in the detoxification processes and the development of oxidative stress in rats with chronic ethanol intoxication of different severity. In experiments on rats using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase participate in changes in liver detoxification function and the development of oxidative stress induced by chronic ethanol intoxication. The direction and severity of changes in arginase activity and liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30% aqueous solution of ethanol (3.5 g 92% ethanol per kg of body weight) in animals under conditions of development of oxidative stress inhibited the activity of arginase and detoxification function of the liver, and the introduction of 10% aqueous solution of ethanol (1.0 g 92% ethanol per kg of body weight) for 2 months leads to an increase in the activity of liver arginase and detoxification processes. The action in the body of the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and lipid peroxidation in the liver during chronic alcohol intoxication caused by intragastric the introduction of ethanol at a dose of 3.5 g / kg for 60 days.

Morphometric features of rat pinealocytes in conditions of chronic ethanol intoxication

Ethanol has chronobiological effects, which are associated with inhibition of melatonin synthesis and secretion and disruption of the sleep-wake cycle. Ethanol is known to cause sleep fragmentation due to frequent awakenings, prolong wakefulness, and reduce the duration of the slow sleep phase. At the same time, changes in the morphology of the pineal gland under chronic exposure to ethanol remain poorly studied. Of particular interest are changes in the basic morphometric parameters of pinealocytes, because they are a marker of the functional state of the pineal gland. The aim of the study was to morphometrically study the features of morphological changes in rat pinealocytes in the physiological norm and in chronic ethanol intoxication. To achieve this goal, we used 20 laboratory male rats: a control group and an experimental group. The control group was under standard vivarium conditions. For the experimental group, alcohol intoxication was modeled by injecting a 40% ethanol solution at the rate of 12 mg/kg of body weight intragastric 4 times a day. The morphometric parameters of pinealocytes were studied on day 30 from the start of the study. According to the results of morphometric measurements, a significant increase in the parameters of light pinealocytes and a decrease in the parameters of dark cells were established. It was determined that the average values of the cytoplasm area of light pinealocytes increase by 54.55% (p<0.05), the area of the nucleus increases by 61.32% (p<0.05), and the area of the nucleolus by 32.84% (p<0.05) compared with the control group. The area of the cytoplasm of dark pinealocytes decreases by 27.2% (p<0.05), and the area of the nucleus by 37.33% (p<0.05). Changes in the ratio of light and dark pinealocytes were also noted. An increase in the number of active light cells by 8.17% was found. The detected morphometric changes indicate high functional activity of cells, which has a compensatory nature in response to apoptosis of pinealocytes.

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE.

Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2, a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-β1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.

REMODELING OF THE DUCT SYSTEM OF THE RAT SUBMANDIBULAR SALIVARY GLANDS IN CHRONIC ETHANOL INTOXICATION

The aim: To determine the dynamics of changes in metric parameters of the duct system of rat submandibular glands in normal conditions and chronic ethanol intoxication. Materials and methods: 50 albino outbred rats were involved in the experiment. 10 animals were assigned in the control group, 40 animals - in the experimental group. Animals were sacrificed on 5, 9, 12 and 30 days by overdose of thiopental anesthesia. Pieces of the submandibular glands were embedded into epon-812 according to the conventional technique. Results: On day 5 of the experiment the lumen diameter of intercalated duct reduced by 9,15 % (р <0,05). The lumen diameter of the striated ducts was by 5,29 % significantly greater than the values in controls (р <0,05). The lumen diameter of the granular ducts reduced by 2,45 % (р <0,05). On day 30 of the experiment the height of the epithelial cells of the intercalated ducts was by 8,47 % significantly less (р <0,05), the height of the epithelial cells of the striated ducts was by 12,27 % less (р <0,05) and the height of the epithelial cells of the granular ducts was by 11,96 % less (р <0,05) than the values in controls. Conclusions: No recovery of parameters occurs by day 30 of the experiment, indicating the depletion of the secretory epithelium of the duct system, due to dystrophic changes caused by vascular disorder in the microvasculature.

TURMERIC EXTRACT IN CORRECTION OF NERVOUS AND IMMUNE SYSTEMS FUNCTIONAL ACTIVITY PARAMETERS IN EXPERIMENTAL ALCOHOLISM

The purpose of this work was to study the effect of turmeric extract on behavior indicators, the severity of the cellular immune response in animals in a state of experimental alcoholism. Experimental models: mouse males (CBAxC57Bl/6)F1 three months of age (n = 60). Alcohol dependence in experimental animals was formed by the method of 6-month soldering with a 10% ethanol solution. In the control groups, the animals received per os water or 10% ethanol solution, in the experimental group - an extract of turmeric powder in a solution of ethanol. Mice behavior was assessed in the “open field” test. The severity of the cellular immune response to sheep erythrocytes was assessed by the intensity of the development of a delayed-type hypersensitivity reaction.It was found that the use of turmeric extract against the background of taking ethanol solution in animals with experimental alcoholism leads to the stimulation of behavior and the increase of the cellular immune response to the level characteristic of healthy animals of the corresponding age.Results indicates the protective effect of turmeric on a number of parameters of the functional activity of the nervous and immune systems during chronic ethanol intoxication.

PATHOMORPHOLOGICAL CHANGES IN THE LIVER IN CASE OF POISONING WITH ETHANOL

The article analyzes the data of autopsy and pathohistological examination of persons who died from ethanol poisoning against the background of various forms of alcoholic liver damage – adaptive hepatopathy (AGP), steatosis (AS), hepatitis (AG), cirrhosis (AC); assesses the morphological changes of the liver. New data on localization, character, degree of steatosis and fibrosis in liver acinuses were obtained. The results of the study can be used as additional criteria for the diagnosis of acute and chronic ethanol intoxication, which allows to objectify the expert conclusions in the production of forensic medical examination (research) of the corpse.

MORPHOMETRIC DESCRIPTION OF THE EXCHANGE SEGMENT OF MICROVASCULATURE OF RATS’ SALIVARY GLANDS IN NORMAL CONDITIONS AND CHRONIC ETHANOL INTOXICATION

Introduction: The state of the segments of the microvasculature, especially exchange one, has a significant effect on the organs' functions. The results of it's research can be objectified by morphometric method. The aim: to determine the dynamics of changes in metric indices of the exchange segment of microvasculature of rats' submandibular glands in normal conditions and in chronic ethanol intoxication. Materials and methods: 45 albino rats were involved into study. Intact group (n=5) animals were administered with NaCl isotonic solution 4 times a day directly into the stomach. Experimental group (n=40) animals were administered with 40° ethanol 4 times a day directly into the stomach. Animals were sacrificed on 5, 9, 12 and 30 days by overdose of thiopental anesthesia. Lobules of submandibular glands were embedded into epon-812 according to standard procedure. Results: On day 5 of the experiment the outer diameter of the capillary wall significantly reduced (4,91±0,02 μm), that is 19,5 % less than the values in controls (р<0,05). On day 9 of the experiment it was 15,2 % lower than the value of control group (р>0,05). On day 30 of the experiment the outer capillary diameter was 8 % lower compared to controls (р<0,05). Conclusions: The early observation showed vasodilatation, confirmed by the constriction of the outer diameter and lumen diameter, accompanied by the thickening of the vascular wall under the influence of chronic ethanol intoxication. The indices did not come to normal values by the 30-th day of the experiment.