Toxic Effects Of Ethanol Research Articles

Peptidergic and adenosinergic drugs administration to comatose patients caused by alcohol consumption on early hospital period

Introduction. Medical care for patients diagnosed with the toxic effect of ethanol (according to ICD-10 code T51.0) it turns out to be in specialized toxicological centers or in emergency departments of multidisciplinary hospitals. The purpose of this study was to study the effectiveness of the drug моликсан® (molixаn) at different levels of medical care for patients diagnosed with the toxic effect of ethanol. Material and method. 128 patients were included in the study, of which 76 patients were taken to the emergency department of St. Petersburg State Medical Institution "Alexandrovskaya Hospital" and 52 patients were taken to the intensive care unit No. 11 of the St. Petersburg Scientific Research Institute of Emergency Medicine named after I.I. Dzhanelidze. All patients met the inclusion criteria: age 18–60 years; impaired consciousness of alcoholic genesis 21–30 points on the Glasgow–Pittsburgh coma scale (PBSS: Pittsburg Brain Stem Score, Kelsey S.F., et al. 1991); ethanol concentration in the blood is more than 2.5%. 72 patients were included in the моликсан® group, 56 patients in the Placebo group. Results. The use of the drug моликсан® has a positive effect on the dynamics of restoring the level of consciousness, which is reflected in higher values of the Glasgow–Pittsburgh scale after 1, 3 and 6 hours from the start of therapy (p<0.01), reducing the period of stay of the patient in a coma from 150 [75; 178] minutes to 60 [50; 161.5] minutes (p<0.05) and restoration of consciousness to a clear level after 3.5± 0.3 hours (p<0.05).It was also revealed, that in the group of patients using моликсан®, normalization of heart rate (p<0.05) and a decrease in the frequency and severity of tremor (p<0.05) were noted. The hepatoprotective efficacy of моликсан® was shown, which manifested itself in a decrease in ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin (p<0.001). Limitations. The clinical efficacy of моликсан® in the toxic effects of severe ethanol was carried out in patients with depression of consciousness and elevated levels of ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin, which indicated the presence of alcoholic hepatopathy. Conclusion. The conducted study showed the expediency of using моликсан® at a dosage of 3.0 mg/kg intravenously with the toxic effect of ethanol of moderate and severe severity of the disease.

Potential Targets for the Protective Effect of Astaxanthin on Ethanolinduced Damage in Rat Liver Mitochondria.

Alcohol intoxication leads to multiple degenerative disorders in the structure and function of mitochondria. The mechanisms underlying these disorders, as well as ways to prevent them, are an urgent task in biomedicine. We investigate the mechanism of the positive effect of AX on rat liver mitochondria after chronic alcohol administration and suggest the targets of its effects. In this work, we continued our studies of astaxanthin (AX) as a possible protector of mitochondria from the toxic effects of ethanol. In our experiments, we used the Lieber-DeCarly model of chronic alcohol intoxication, which allows high-dose alcohol intake. Four groups of animals were used in the experiments: group 1 (control), group 2 (treated with AX), group 3 (treated with ethanol), and group 4 (treated with ethanol and AX together). Rat liver mitochondria (RLM) were isolated by the standard method modified in our laboratory. A multifunctional chamber with built-in electrodes was used to determine mitochondrial functions. Electrophoresis followed by Western blot analysis was used to detect mitochondrial proteins. Statistical significance was calculated using t-test Student-Newman- Keuls test. AX has been shown to have a positive effect on the functioning of the mitochondrial permeability transition pore (mPTP), the regulation of signaling pathways, as well as mitochondrial dynamics. It was found that AX is able to suppress the degenerative effect of alcohol on liver mitochondria. Targets for the protective action of AX in rat liver mitochondria (RLM) have been proposed. The discovered protective effect of AX on liver mitochondria during alcohol damage may contribute to the development of new strategies for the treatment of alcohol- induced damage.

Влияние фитохимического и антиоксидантного составов необработанных водных экстрактов Chlorella vulgaris на рост Saccharomyces cerevisiae в спиртовой среде

Chlorella vulgaris is rich in secondary metabolites that defend against environmental stress and aid in detoxification. In particular, bioactive compounds extracted from C. vulgaris may enhance the growth of microorganisms and detoxify them in an ethanolic medium. We aimed to effectively extract and characterize bioactive compounds found in C. vulgaris and further test them for their beneficial effects on the growth of Saccharomyces cerevisiae cultured in an ethanolic medium. Bioactive compounds in C. vulgaris were extracted using ultrasound and water as solvents. The extracts were analyzed for total phenol and flavonoid contents as part of their phytochemical composition. Their DPPH radical activity and Hydrogen peroxide scavenging activity were examined to determine their antioxidant properties and protective potential for S. cerevisiae in an ethanolic medium. Further, the extracts were added at 0.1, 0.5, 1, 2, 3, and 4% w/v concentrations into S. cerevisiae culture induced with 1% v/v ethanol for 23 days. The yeast cells’ density and viability were measured after 2, 5, 9, 13, 17, and 23 days. The extracts of C. vulgaris were rich in phenols and flavonoids, which are important bioactive compounds. Higher concentrations of the extracts increased total phenols up to 47.67 GAE mg/L and total flavonoids up to 218.67 QE mg/L. The extracts’ antioxidant composition showed high DPPH activity (70.12%) and H2O2 scavenging activity (4.97%). After 23 days, the samples treated with C. vulgaris extracts maintained a high viability of the yeast cells. In particular, the samples with 2, 4, 0.1, and 1% of the extract had a cell viability of 95.75, 94.04, 89.15, and 74%, respectively. The positive control (1% ethanol alone) and negative control (yeast alone) had 47.71 and 21.01% viability, respectively. This drastic reduction in viability was due to lysis of the yeast cells caused by ethanol. Ultrasound extraction with water as a solvent produced abundant beneficial secondary metabolites from C. vulgaris. The addition of C. vulgaris extract increased the viability and cell density of S. cerevisiae after 27 days, thereby protecting the yeast cells from the toxic effects of ethanol.

Features of the circadian rhythm in the size of mitochondria of rat hepatocytes under conditions of dark deprivation and chronic alcohol intoxication

Background Circadian rhythms (CR) of functions and processes in the body are normally strictly coordinated with each other and with environmental factors, which ensures the maintenance of the functioning of the organs and systems of the body at an optimal level. However, we have not found any studies devoted to the study of CR of hepatocyte organelles under experimental conditions. Aim of study Study of the daily dynamics of the cross-sectional area of hepatocyte mitochondria in rats under conditions of dark deprivation, chronic alcohol intoxication and the combined effect of these factors. Materials and methods The work was performed on 80 males and 80 females Wistar rats, divided into 4 groups of each sex. Group 1 was kept under a fixed light regime; The 2nd group was kept under conditions of dark deprivation; the 3rd group was kept in the same conditions as the animals of the control group, but were subjected to chronic alcohol intoxication; Group 4 was kept in conditions of dark deprivation and subjected to chronic alcohol intoxication. Liver samples, after fixation and wiring, were analyzed using a transmission electron microscope. Micromorphometric methods were used to assess the mitochondrial apparatus of hepatocytes. Results In hepatocytes of rats from experimental groups of both sexes, CR of the cross-sectional area of mitochondria with similar parameters was detected. Dark deprivation and chronic alcohol intoxication, acting both separately and together, cause a restructuring of the mitochondrial size distribution, which is more pronounced in males. Conclusion The study indicates that the CR of mitochondrial size is dependent on the lighting regime and the toxic effect of ethanol and its metabolites. The size ranges of mitochondria in hepatocytes of females, compared to males, are more resistant to the effects of dark deprivation and alcohol intoxication.

COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

The effects of omega-3 fatty acids on antioxidant enzyme activities and nitric oxide levels in the cerebral cortex of rats treated ethanol.

The toxic effect of ethanol on the cerebral cortex and protective effects of omega-3 fatty acids against this neurotoxicity were investigated. Twenty eight male Wistar-albino rats were divided into 4 groups. Rats of the ethanol and ethanol withdrawal groups were treated with ethanol (6 g/kg/day) for 15 days. Animals of the ethanol+omega-3 group received omega-3 fatty acids (400 mg/kg daily) and ethanol. In rats of the ethanol group SOD activity was lower than in animals of the control group. In rats treated with omega-3 fatty acids along with ethanol SOD, activity increased. GSH-Px activity and MDA levels in animals of all groups were similar. In ethanol treated rats NO levels significantly decreased as compared to the animals of the control group (6.45±0.24 nmol/g vs 11.05±0.53 nmol/g, p.

Histologic changes in the liver and kidney tissues of rats with acute alcohol injury and metabolic correction

Annotation. The liver and kidneys are among the organs that often suffer from the toxic effects of ethanol. The issue of drug correction of alcoholic organ damage, and in particular the role of H2S, remains insufficiently studied. The aim of the study was to evaluate the role of quercetin, hydrogen sulphide donor NaHS and their combination in the correction of morphological changes in the liver and kidneys of rats with acute alcohol injury (AAI). The study was conducted on 25 white male rats weighing 120-130 g, divided into five groups (5 rats in each group). Animals of groups 2-5 were modelled with AAI by intragastric administration of 40% ethanol at a dose of 20 ml/kg for 7 days. In order to correct the AAI, animals of group 3 were administered quercetin (100 mg/kg, intraperitoneally, once/day, for 7 days), group 4 – the hydrogen sulphide donor NaHS-H2O (3 mg/kg, intraperitoneally, once/day, for 7 days), group 5 – both quercetin and NaHS-H2O in the above doses. Animals of group 1 (control) received an equivalent amount of solvents. Histological examinations were performed according to conventional methods. It has been established that in the liver of rats with AAI there are disturbances in the lobular structure, radial ordering of the hepatic beams, signs of inflammation, hypertrophy and fatty infiltration of hepatocytes. In the kidneys, signs of renal glomerular fragmentation, vascular glomerular compaction, tubular epithelial dystrophy, and inflammation are found. Some improvements in the histological structure of the liver and kidneys were observed with quercetin, but they were inferior to those observed with NaHS. Combined therapy with quercetin and NaHS was most effective in restoring the normal structure of the liver and kidneys of rats: the radial arrangement of hepatic beams was restored, the nuclear cytoplasmic index increased, signs of fatty degeneration of hepatocytes and renal epithelial dystrophy decreased, and the activity of the inflammatory response in the organs decreased. The obtained results histologically confirm the feasibility of using hydrogen sulphide donors to enhance the hepatoprotective and nephroprotective effects of quercetin in the setting of AAI.

Key trends in elderly people mortality from the toxic effects of ethanol

This article including an analysis of trends in mortality of the elderly population (from 60 to 75 years, according to the classification of the World Health Organization) to various criteria from ethyl alcohol poisoning. We studied the dynamics of mortality the elderly people from the toxic effects of ethanol, as well as correlations and causal relationships were found between the frequency of death from the indicated cause and gender, age, and the place where the body was found (urban or rural). The features of filling in a medical certificate of death with the initial (presumed) and final cause of death "toxic effects of ethanol" were revealed. The place of direct alcoholic mortality of the elderly population in the total mortality from all causes and ethanol poisoning in the region of the Chelyabinsk region for the period from 2010 to 2021 was determined.
 For citation: Botova, MA. Key trends in mortality of the elderly people from the toxic effects of ethanol. City Healthсare. 2022;3(4): 92–99 doi:10.47619/2713-2617.zm.2022.v.3i4;92–99

Ethanol tolerance of Clostridium thermocellum: the role of chaotropicity, temperature and pathway thermodynamics on growth and fermentative capacity

BackgroundClostridium thermocellum is a promising candidate for consolidated bioprocessing of lignocellulosic biomass to ethanol. The low ethanol tolerance of this microorganism is one of the remaining obstacles to industrial implementation. Ethanol inhibition can be caused by end-product inhibition and/or chaotropic-induced stress resulting in increased membrane fluidization and disruption of macromolecules. The highly reversible glycolysis of C. thermocellum might be especially sensitive to end-product inhibition. The chaotropic effect of ethanol is known to increase with temperature. This study explores the relative contributions of these two aspects to investigate and possibly mitigate ethanol-induced stress in growing and non-growing C. thermocellum cultures.ResultsTo separate chaotropic from thermodynamic effects of ethanol toxicity, a non-ethanol producing strain AVM062 (Pclo1313_2638::ldh* ∆adhE) was constructed by deleting the bifunctional acetaldehyde/alcohol dehydrogenase gene, adhE, in a lactate-overproducing strain. Exogenously added ethanol lowered the growth rate of both wild-type and the non-ethanol producing mutant. The mutant strain grew quicker than the wild-type at 50 and 55 °C for ethanol concentrations ≥ 10 g L−1 and was able to reach higher maximum OD600 at all ethanol concentrations and temperatures. For the wild-type, the maximum OD600 and relative growth rates were higher at 45 and 50 °C, compared to 55 °C, for ethanol concentrations ≥ 15 g L−1. For the mutant strain, no positive effect on growth was observed at lower temperatures. Growth-arrested cells of the wild-type demonstrated improved fermentative capacity over time in the presence of ethanol concentrations up to 40 g L−1 at 45 and 50 °C compared to 55 °C.ConclusionPositive effects of temperature on ethanol tolerance were limited to wild-type C. thermocellum and are likely related to mechanisms involved in the ethanol-formation pathway and redox cofactor balancing. Lowering the cultivation temperature provides an attractive strategy to improve growth and fermentative capacity at high ethanol titres in high-cellulose loading batch cultivations. Finally, non-ethanol producing strains are useful platform strains to study the effects of chaotropicity and thermodynamics related to ethanol toxicity and allow for deeper understanding of growth and/or fermentation cessation under industrially relevant conditions.

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.

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.

The multiple roles of lipid metabolism in yeast physiology during beer fermentation.

The ability of brewing yeasts (Saccharomyces cerevisiae and Saccharomyces pastorianus) to cope with the toxic effects of ethanol during beer fermentation depends on the modulation of lipid and lipid droplets (LDs) biosynthesis, which affects membrane fluidity. However, it has been demonstrated that lipids and LDs can modulate different biological mechanisms associated to ethanol tolerance, including proteostasis and autophagy, leading to the hypothesis that lipid and LDs biosynthesis are integrative processes necessary for ethanol tolerance in yeast. Supporting this hypothesis, a transcriptome and systems biology analyses indicated the upregulation of autophagy, lipid biosynthesis, and proteostasis (ALP)-associated genes in lager yeast during beer fermentation, whose respective proteins interact in a shortest-pathway ALP network. These results indicated a cross-communication between various pathways linked to inter-organelle autophagy, lipid metabolism, and proteostasis (ALP) during lager beer fermentation, thus highlighting the importance of lipids for beer fermentation.

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.

Assessment of BMP responses in an in vitro model of acute ethanol toxicity

The assay presented here was designed to assess the immediate effects of ethanol (EtOH) exposure on intracellular signaling activated by BMPs (Bone Morphogenetic Proteins). Previous reports of the relationship between EtOH exposure and BMP-dependent signaling have primarily assessed the expression of individual BMPs, changes in BMP target genes or effects on the phosphorylation level of key downstream mediators after days or weeks of in vivo EtOH exposure. What happens to BMP-stimulated signaling immediately following exposure to EtOH remains largely unexplored. Here, the early events of BMP-evoked intracellular signaling were examined in an in vitro model of acute EtOH toxicity. The BMP/Ethanol Stimulation Assay involved first stimulating cultured cells with recombinant BMPs. BMP-evoked intracellular signaling was then allowed to develop for 30 minutes. Next, the cells were exposed to a range of EtOH concentrations for an additional 30 minutes. Finally, the cultures were processed for Western blot analysis or immunofluorescent labeling.This short-term assay:• Permits investigation of EtOH exposure during the initial signaling events downstream of BMP receptor activation• Enables assessment of how the presence of BMPs might protect against cellular injury caused by toxic EtOH levels

Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product

Effects of ethanol ingestion on aversive conditioning in honey bees (Apis mellifera L.).

Ethanol consumption has been shown to have many deleterious effects, including behavioral alterations, motor deficits, reduction in inhibition, and alteration of neurochemical expression. These effects occur in the wide variety of species that consume ethanol. Although studies have examined aversive conditioning in honey bees (Apis mellifera), few have examined the role of intoxication on the acquisition of learning in such paradigms. The current study continues a line of research using honey bees as a model to explore the behavioral effects of ethanol toxicity. A passive avoidance task is used to explore how increasing dosages of ethanol affects the ability of honey bees to perform this task. The results show that honey bees exposed to higher concentrations of ethanol have slower passive avoidance acquisition than bees exposed to lower concentrations under the same conditions. Bees not experiencing aversive stimuli displayed no difference from baseline behavior when exposed to varying concentrations of ethanol. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Current View on the Mechanisms of Alcohol-Mediated Toxicity.

Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.

Assessment of Ethanol-Induced Toxicity on iPSC-Derived Human Neurons Using a Novel High-Throughput Mitochondrial Neuronal Health (MNH) Assay.

Excessive ethanol exposure can cause mitochondrial and cellular toxicity. In order to discover potential counteracting interventions, it is essential to develop assays capable of capturing the consequences of ethanol exposure in human neurons, and particularly dopaminergic neurons that are crucial for the development of alcohol use disorders (AUD). Here, we developed a novel high-throughput (HT) assay to quantify mitochondrial and neuronal toxicity in human dopaminergic neuron-containing cultures (DNs) from induced pluripotent stem cells (iPSCs). The assay, dubbed mitochondrial neuronal health (MNH) assay, combines live-cell measurement of mitochondrial membrane potential (MMP) with quantification of neuronal branching complexity post-fixation. Using the MNH assay, we demonstrated that chronic ethanol exposure in human iPSC-derived DNs decreases MMP and neuronal outgrowth in a dose-dependent manner. The toxic effect of ethanol on DNs was already detectable after 1 h of exposure, and occurred similarly in DNs derived from healthy individuals and from patients with AUD. We next used the MNH assay to carry out a proof-of-concept compound screening using FDA-approved drugs. We identified potential candidate compounds modulating acute ethanol toxicity in human DNs. We found that disulfiram and baclofen, which are used for AUD treatment, and lithium caused neurotoxicity also in the absence of ethanol, while the spasmolytic drug flavoxate positively influenced MNH. Altogether, we developed an HT assay to probe human MNH and used it to assess ethanol neurotoxicity and to identify modulating agents. The MNH assay represents an effective new tool for discovering modulators of MNH and toxicity in live human neurons.

CAPABILITIES OF HOSPITAL EMERGENCY DEPARTMENTS IN THE TREATMENT OF PATIENTS WITH A DIAGNOSIS OF “TOXIC EFFECT OF ETHANOL”

The relevance of a subject is conditioned by the extreme importance of the medical and social issues of providing medical care services to patients with acute alcohol intoxication. This research is conducted to find ways to optimize medical care services for patients with the diagnosis “toxic effect of ethanol” (ICD-10-CM code T51.0). For this study, was analysed: course of 13172 clinical cases and the possibility of treating this pathology in the hospital emergency departments. Statistical and analytical methods were used to study data from the medical information system of The Saint Petersburg Research Institute of Emergency Medicine n. a. I. I. Dzhanelidze. As a result of the study the place of treatment of patients with diagnose “toxic effect of ethanol” was determined: for mild and moderate patient — emergency departments of multi-specialty hospitals, and for severe patient — in specialized acute poisoning treatment Center.