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Ethanol has been demonstrated to exert profound effects upon cells and tissues via multiple mechanisms. One recently appreciated means by which cells can communicate with other cells is via the production and release of extracellular vesicles. Though smaller exosomes have been demonstrated to be released in response to ethanol exposure, the ability of ethanol to modulate the generation and release of larger microvesicle particles (MVP) is lesser studied. The present studies examined the ability of exogenous ethanol to generate MVP with a focus on skin cells. Acute ethanol exposure resulted in augmented MVP release in keratinocytes and in the skin and blood of mice. Unlike other stimuli such as ultraviolet B radiation or thermal burn injury, ethanol-mediated MVP release was independent of the Platelet-activating Factor receptor (PAFR). However, ethanol pretreatment was found to augment thermal burn injury-induced MVP in a PAFR-dependent manner. These studies provide a novel mechanism for ethanol-mediated effects, that could be relevant in the significant toxicity associated with thermal burn injury in the setting of alcohol intoxication.

Stress is a ubiquitous part of life that disrupts cellular function and, if unresolved, can irreparably damage essential biomolecules and organelles. All organisms can experience stress in the form of unfavorable environmental conditions including exposure to extreme temperatures, hypoxia, reactive oxygen species, alcohol, or shifts in osmolarity. To survive, organisms must sense these changes then react and adapt. One highly conserved adaptive response to stress is through protein sumoylation, which is a post-translational modification by the small ubiquitin-like modifier (SUMO) protein. In this study, we examine the effects of acute ethanol stress on protein sumoylation in the budding yeast Saccharomyces cerevisiae. Although ethanol induces protein sumoylation, the targets and roles of sumoylation are largely unknown. Here, we found that cells exhibit a transient sumoylation response after exposure of cells to ≤ 7.5% volume/volume ethanol. The response peaks at 15 minutes and resolves by 60 minutes, indicating that cells have an adaptive response to low concentrations of ethanol. By contrast, the sumoylation response becomes chronic at 10% ethanol stress with no resolution by 60 minutes. To identify key targets of ethanol-induced sumoylation, we performed mass spectrometry analyses and identified 18 proteins with increased sumoylation after acute ethanol exposure, with 15 identified as known chromatin-associated proteins. Two of these proteins are the chromatin structural proteins Smc5 and Smc6, which are sumoylated by the activity of the SUMO ligase Mms21. Ethanol-induced Smc5/6 sumoylation occurs during G1 and G2M phases of the cell cycle but is abrogated during S phase despite the fact that other proteins are sumoylated during this phase. Acute ethanol exposure leads to formation of Rad52 foci indicating DNA damage similar to that observed with the addition of methyl methanesulfonate (MMS), which is an alkylating agent that damages DNA. Whereas MMS exposure induces the intra-S phase DNA damage checkpoint as observed by Rad53 phosphorylation, ethanol exposure does not induce the intra-S phase checkpoint and prevents Rad53 phosphorylation when added with MMS. From these results, we propose that ethanol induces a structural change in chromatin, possibly through DNA damage, and this causes sumoylation of conserved chromatin-associated proteins, including Smc5 and Smc6.

BACKGROUND: The medial prefrontal cortex (mPFC) is a brain region involved in the evaluation and selection of motivationally relevant outcomes. Neural activity in mPFC is altered following acute ethanol (EtOH) use and, in rodent models, doses as low as 0.75 g/kg yield cognitive deficits. Deficits in decision-making following acute EtOH are thought to be mediated, at least in part, by decreases in mPFC firing rates (FRs). However, the data leading to this conclusion have been generated exclusively in anesthetized rodents. The present study characterizes the effects of acute EtOH injections on mPFC neural activity in awake-behaving rodents. METHODS: Awake-behaving and anesthetized in vivo electrophysiological recordings were performed. We utilized three groups: the first received two saline injections, the second received a saline injection followed by 1.0 g/kg EtOH, the last received saline followed by 2 g/kg EtOH. One week later an anesthetized recording occurred where a saline injection was followed by an injection of 1.0 g/kg EtOH. RESULTS: The anesthetized condition showed robust decreases in neural activity and differences in up-down state dynamics. In the awake-behaving condition, FRs were grouped according to behavioral state: moving, not moving, and sleep. The differences in median FRs were found for each treatment and behavioral state combination. A FR decrease was only found in the 2.0 g/kg EtOH treatment during not moving states. However, robust decreases in FR variability were found across behavioral state in both the 1.0 g/kg and 2.0 g/kg EtOH treatment. Sleep was separately analyzed. EtOH modulated the up-down states during sleep producing decreases in FRs. CONCLUSIONS: In conclusion, the changes in neural activity following EtOH administration in anesthetized animals are not conserved in awake-behaving animals. The most prominent difference following EtOH was a decrease in FR variability suggesting that acute EtOH may be affecting decision-making via this mechanism.

Ethanol intoxication is analyzed from the point of ethanol interaction with receptors and enzymes. Ethanol dependence is based on neurochemical misbalance, which is different in acute ethanol intoxication and withdrawal. It is shown that the clinical manifestation of ethanol intoxication and its complications depends on ligand-receptor and enzyme imbalances. Pharmacological approaches to the treatment of acute ethanol intoxication and its complications at the pre-hospital stage and in the emergency, unit are discussed.

Chronic alcoholism and acute ethanol poisoning have significant effects on the central nervous system. These effects can be divided into two groups. The first effect is the volume loss associated with a toxic effect on neurons mediated by neurotransmitters and/or receptors and electrolytes, and the secondary effects are associated with the sequela of liver cirrhosis such as hepatic encephalopathy and coagulopathies, and the problems in the gastrointestinal tract leading to impairment of vitamin uptake, ultimately leading to Wernicke-Korsakoff syndrome. Herein, we report a 68-year-old male patient who presented to the emergency room with confusion associated with acute ethanol poisoning on the basis of chronic alcoholism. A brain computed tomography (CT) scan revealed symmetrical hemorrhagic necrosis in bilateral frontal regions. In our case, vasculopathies and infectious etiology were excluded through cerebral and carotid vertebral CT angiography, examinations, and laboratory findings. Investigation of the cause of this atypical radiographic finding revealed that ethanol ingestion leads to increased risk for hypertension, as well as cerebral hemorrhage by resulting in coagulation dysfunction; it triggers P53- and neuron-specific enolase- mediated apoptosis and necrosis, thereby resulting in neuronal damage. Acute and chronic use of ethanol has specific effects on the frontal lobe of the brain. The findings are discussed in light of the relevant literature.

The brain is particularly vulnerable to ethanol effects during its growth spurt. Outcomes of early ethanol exposure such as hyperactivity have been extensively investigated; however, persons with fetal alcohol spectrum disorder frequently have social impairments and are heavy drinkers. Despite that, scant information is available regarding the neurobiological basis of these latter behavioral issues. Here, Swiss mice exposed to ethanol (Etoh, 5 g/kg i.p., alternate days) or saline during the brain growth spurt [postnatal day (PN) 2 to 8] were used to assess social behavior after an ethanol challenging during adolescence. At PN39, animals were administered with a single ethanol dose (1 g/Kg) or water by gavage and were then evaluated in the three-chamber sociability test. We also evaluated corticosterone serum levels and the frontal cerebral cortex serotoninergic system. Etoh males showed reductions in sociability. Ethanol challenging reverted these alterations in social behavior, reduced corticosterone levels, and increased the 5-HT2 receptor binding of male Etoh mice. No alterations were observed in 5-HT and 5-HIAA contents. These data support the idea that ethanol exposure during the brain growth spurt impacts social abilities during adolescence, alters ethanol reexposure effects, and suggests that stress response and serotoninergic system play roles in this phenomenon.

The mean population age of the United States continues to increase, and data suggest that by the year 2060 the population of people over the age of 65 will more than double, providing a potentially massive strain on health care systems. Research demonstrates individuals 65 and older continue to consume ethanol, often at high levels. However, preclinical animal models are still being developed to understand how ethanol might interact with the aged population. The current experiments investigated differential body temperature responses in aged rats compared to adult rats and adolescent rats. Aged (19 months of age), adult (70 days of age), or adolescent (30 days of age) male Sprague Dawley rats were administered 1.0 g/kg, 2.0 g/kg, or 3.0 g/kg ethanol, intraperitoneally (i.p.), in a balanced Latin square design. Prior to ethanol administration, a core body temperature via an anal probe was obtained, and then repeatedly determined every 60 min following ethanol exposure for a total of 360 min. In addition, a blood sample was obtained from a tail nick 60, 180, and 300 min following the ethanol injection to investigate the relationship of ethanol levels and body temperature in the same animals. Aged rats had significantly greater reductions in body temperature compared to either adult or adolescent rats following both the 2.0 g/kg and 3.0 g/kg ethanol injection. Additionally, adolescent rats cleared ethanol significantly faster than aged or adult animals. These experiments suggest body temperature regulation in aged rats might be more sensitive to acute ethanol compared to adult rats or adolescent rats. Future studies are needed to identify the neurobiological effects underlying the differential sensitivity in aged rats to ethanol.

Aims Alcohol consumption influences the water balance in the brain. While the impact of chronic alcohol misuse on cerebral water content has been the subject of several studies, less is known about the effects of acute alcohol misuse, with contradictory results in the literature. Therefore, we investigated the effects of acute alcohol intoxication on cerebral water content using a precise quantitative magnetic resonance imaging (MRI) sequence. Methods In a prospective study, we measured cerebral water content in 20 healthy volunteers before alcohol consumption and after reaching a breath alcohol concentration of 1 ‰. A quantitative MRI water mapping sequence was conducted on a clinical 3 T system. Non-alcoholic fluid input and output were documented and accounted for. Water content was assessed for whole brain, grey and white matter and more specifically for regions known to be affected by acute or chronic alcohol misuse (occipital and frontal lobes, thalamus and pons). Changes in the volume of grey and white matter as well as the whole brain were examined. Results Quantitative cerebral water content before and after acute alcohol consumption did not differ significantly (P ≥ 0.07), with changes often being within the range of measurement accuracy. Whole brain, white and grey matter volume did not change significantly (P ≥ 0.12). Conclusion The results of our study show no significant water content or volume change in the brain after recent alcohol intake in healthy volunteers. This accounts for the whole brain, grey and white matter, occipital and frontal lobes, thalamus and pons.

Ethanol consumption is a worldwide problem. Sensitivity to acute effects of ethanol influences the development of chronic ethanol abuse and ethanol dependence. Environmental and genetic factors have been found to contribute to differential effects of acute ethanol. Animal models have been employed to investigate these factors. An increasingly frequently utilized animal model in ethanol research is the zebrafish. A large proportion of ethanol studies with zebrafish have been conducted with adult zebrafish. However, high throughput drug and mutation screens are particularly well adapted to larval zebrafish. These studies are often carried out using the 96-well-plate that allows monitoring large numbers of fish efficiently. Here, we investigate the effects of acute (30 min long) ethanol exposure in 8-day post-fertilization (dpf) old zebrafish. We compare four genetically distinct populations (strains) of zebrafish, measuring numerous parameters of their swim path in two well sizes, i.e., in the 96-well-plate (small volume wells) and in the 6-well-plate (large volume wells). In general, we found that the highest dose of ethanol (1% vol/vol) reduced swim speed, increased duration of immobility, increased turn angle, and increased intra-individual variance of turn angle, while the intermediate dose (0.5%) had a less strong effect, compared to control. However, we also found that these ethanol effects were strain dependent and, in general, were better detected in the larger volume well. We conclude that larval zebrafish are appropriate for quantification of acute ethanol effects and also for the analysis of environmental and genetic factors that influence these effects. We also speculate that using larger wells will likely increase sensitivity of detection and precision in screening applications.

Aim: This study is aimed at investigating the ameliorative efficacy of methanolic extract of Corchorus olitorius leaves against acute ethanol-induced oxidative stress in Wistar rats. Methods: Fresh plants of C. olitorius were harvested from the Institute of Agricultural Research and Training, Ibadan. The leaves were dried and extracted using soxhlet apparatus and methanol as the solvent. The methanol was evaporated in a rotary evaporator at 35°C with a yield of 2.17 g which represents a percentage yield of 8.68%. Twenty adult male Wistar rats with body weight between 120 and 150 g were used for this study. They were randomly divided into four groups of five rats each. Animals in groups 1 and 2 were administered saline solution while those in groups 3 and 4 were administered C. olitorius extract for twenty-one days. The animals were administered the extract and saline solution at a dose of 4 mL per 100 g body weight 12 hourly via oral route of administration. At the end of the treatment, they were fasted overnight and animals in groups 2 and 4 were exposed to a single dose of 70% ethanol at 12 ml/kg body weight to induce oxidative stress. After 12 hours of ethanol administration, the animals were anaesthetized using diethyl ether and were sacrificed. Liver was excised, weighed and homogenized in 50 mmol/L Tris–HCl buffer (pH 7.4) and then centrifuged at 5000 × g for 15 minutes for biochemical analysis. Supernatants were immediately kept frozen for further analysis. Results: Ethanol-induced oxidative stress significantly increased the activities of AST, ALT, LDH, LPO, CAT, SOD and GPX but decrease GSH. These effects were regulated by C. olitorius administration. Conclusion: C. olitorius was able to remedy the effect of ethanol by regulating the oxidative stress biomarkers, thus possesses ameliorative efficacy against ethanol-induced oxidative stress and can protect the body against free radicals arising from oxidative stress.

Ethanol-induced diseases include oxidative mechanisms by which prolonged endoplasmic reticulum (ER) stress results in genesis and accumulation of cytotoxic total fatty acid ethyl esters (FAEEs, non-oxidative metabolites of ethanol). FAEEs participate in the pathogenesis of alcoholic lung disease. Polyunsaturated fatty acids (PUFA) offer a possible protective effect against damage induced by ethanol inhalation. The present study aimed to investigate the protective effect of flaxseed and fish oils administration against toxicity induced by ethanol inhalation. Forty healthy female albino rats were divided into four groups (control, ethanol, flaxseed and fish oils). Lung superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Plasma advanced oxidation end product (AOPP) and phosphatidylinositol 3- kinase (PI3K) were determined. Erythrocyte membrane fatty acids were extracted and fractionated by HPLC. Ethanol inhalation results in significant increase in lung MDA, plasma AOPP and erythrocyte membrane arachidonic acid (AA), linolenic acid (LA), and oleic acid (OA) along with a significant decrease in erythrocyte membrane alpha-linolenic acid (ALA), lung SOD, and plasma PI3K while pretreatment with flaxseed and fish oils daily (1.2 ml/kg) significantly attenuated these parameters. Supplementation of marine PUFAs reduced the oxidative stress induced by ethanol inhalation in experimental animals.

Acute ethanol intoxication has a diversity of clinical pictures that extend from mere euphoria to severe neurological impairment culminating in coma. Although the majority of cases have a reversible and benign course, the situation needs a careful medical monitoring. Authors describe pharmacological aspects of the acute ethanol intoxication, with organs and systems affected during the consumption of exaggerated quantities. Correlations between blood alcohol concentration and neurological symptomatology are given, and a brief discussion of the criteria for the acute intoxication is made. The fact that this occurrence has been of little attention is due not only to the reversibility of the majority of symptoms, but also because that medical research has been ever since focused more on chronic diseases related to alcohol abuse, withdrawal syndrome and recently with hangover as an independent situation. With no specific antidote actually at hand, treatment is symptom-oriented and the pharmacological armamentarium is richer when it comes to dealing with withdrawal, abstinence and other chronic complications of ethanol abuse.

Introduction: Alcohol abuse is one of the grave social and medical problems in many countries, including Russia. Alcohol not only negatively affects health, social and family relationships, but also a person’s performance. Hangover, which is a one of the negative consequences of alcohol intake, is a complex of neurological and somatic symptoms that occur when ethanol is almost completely metabolized to acetaldehyde. This condition, despite the severity and potential economic damage, remains poorly understood, and there are no effective medicines to treat it. Aim: to provide an experimental basis for the possibility of using N-acetylcysteine (NAC), a precursor of glutathione, as a medicine for prevention of the neurological and cognitive impairments due to alcohol intoxication. Materials and Methods: The study used male Wistar rats, which were intraperitoneally injected with ethanol at a dose of 3 g/kg to simulate acute ethanol intoxication. Sixty minutes before the injection, the animals from the experimental groups were gavaged with NAC (1 g/kg) or with an equivalent volume of saline. Immediately after awakening and 3 h after it, the animals were assessed for neurological deficits, motor skills, spontaneous motor activity, and cognitive functions. After the completion of the behavioral tests, the animals were euthanized to assess the level of glutathione, triglycerides (TGs), and malonic dialdehyde (MDA) in liver homogenates, and to determine the activity of enzymatic antioxidant systems and serum aminotransferases. Results and Discussion: The ethanol intoxication in the animals from the control group was associated with pronounced signs of neurological and cognitive impairments, including low spontaneous motor and exploratory activity, impaired fine motor skills in the adhesive test, and cognitive function decline in the Morris water maze test. The rats which had received NAC before ethanol injection demonstrated better fine motor skills in the adhesive test, a higher level of spontaneous motor activity and better performance in the Morris water maze test (in comparison to the animals treated with saline before alcohol intoxication). In the animals which had received NAC, the levels of glutathione, MDA, and TGs, as well as the activity of liver antioxidant enzymes, were closer to the values of the intact rats to a greater extent than in the animals that had been injected with ethanol and received saline. Conclusion: Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunction.

Propensity to drink alcohol and to initiate binge drinking behavior is driven by genetic factors. Recently, we proposed an original animal model useful in the study of voluntary binge-like drinking (BD) in outbred Long-Evans rats by combining intermittent access to 20% ethanol in a two-bottle choice (IA2BC) paradigm to 15-min daily sessions of 20% ethanol operant self-administration. We sought to compare three strains of outbred rats (Long-Evans, Sprague-Dawley, and Wistar) in our BD model. Because we found different propensity to BD between strains, we also sought to test interstrain differences using another procedure of two acute ethanol exposures known to alter long-term depression of hippocampal synaptic plasticity. Our results demonstrate that in both IA2BC and operant procedures, the Long-Evans strain consumed the highest, Wistar the lowest amount of ethanol, and the Sprague-Dawley was intermediate. Long-Evans rats were also the fastest consuming with the shortest time to reach 50% of their maximum consumption in 15 min. When we tested the acute effects of ethanol, long-term depression in hippocampus was abolished specifically in Long-Evans rats with no impact in the two other strains. Thus, our study reveals that the Long-Evans strain is the ideal strain in our recently developed animal model useful in the study of BD. In addition, with the other paradigm of forced acute ethanol exposure, the Long-Evans strain displayed an increase in sensitivity to the deleterious effect of BD on hippocampal synaptic plasticity. Further studies are needed in order to investigate why Long-Evans rats are more prone to BD.

The study establishes a link between alcoholism, inflammation state, and melatonin synthesis. The aim of our study was to evaluate the effects of melatonin on changes in the relationships between oxygen consumption (using NADH- or FAD-generated substrates of mitochondrial respiration), activities of lysosomal enzymes, such as alanyl aminopeptidase (AAP), leucyl aminopeptidase (LAP), β-N-acetylglucosaminidase (NAG), and acid phosphatase (AcP), biomarkers of oxidative stress estimated by the 2-thiobarbituric acid reactive substance (TBARS) level as a biomarker of lipid peroxidation, carbonyl derivatives as biomarkers of oxidatively protein damage, and biomarkers of energy metabolism during acute ethanol-induced stress (AES), and a low-dose lipopolysaccharide (LPS)-induced inflammatory responses in mice. Biochemical assays of lysosomal enzymes, biomarkers of oxidative stress, and parameters of energy metabolism (activities of alanine- and aspartate aminotransferases, succinate dehydrogenase, levels of lactate and pyruvate) were carried out in eight groups: 1) untreated control, 2) melatonin treatment (Mel, 10 mg/kg b.w., 10 days), 3) acute ethanol-induced stress (AES, 0.75 g/kg b.w., 10 days), 4) AES model with previous Mel treatment (10 mg/kg b.w., 10 days), 5) LPS-induced inflammation (injected once intraperitoneally, 150 μg/mouse), 6) LPS-induced inflammation with previous Mel treatment (10 mg/kg b.w., 10 days), 7) LPS-induced inflammation with AES model, 8) LPS-induced inflammation with AES model and Mel treatment (10 mg/kg b.w., 10 days). Oxidative stress caused by acute ethanol-induced intoxication and low-dose LPS-induced inflammation lead to structural and functional impairments, with alterations in oxygen consumption more prominent in kidneys than liver. Melatonin treatment had significant effects on mitochondrial oxidation of the NADH-generated substrate, and it also decreased mitochondrial ability to oxidize FAD-generated substrate and mitochondrial coupling in both LPS- and AES-induced oxidative stress. Melatonin exerts significant effect on the oxidation of the NAD-generated substrates. The increased lipid peroxidation and De Ritis ratio suggest damage to intracellular membrane integrity with combined effects of ethanol and LPS-induced toxicity, which can potentially result in irreversible tissue damage. Melatonin prevents lysosomal destruction of liver tissue and, to greater extent, kidney tissue during AES with simultaneous LPS exposure by limiting increased activity of lysosomal enzymes and resulting oxidative stress.

Background: Ethanol have been linked to atrophic gastritis and gastric carcinoma. Although it is well known that ethanol can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood.Results: Here we used gastric organoids to show that ethanol permeabilized the apical membrane of gastric parietal cells and induced ezrin hypochlorhydria. The functional consequences of ethanol on parietal cell physiology were studied using organoids. Gastric organoids were pre-incubated in the basic medium or with EGTA or E64 , and incubated at 37℃ in either medium alone, or medium containing 6% ethanol. We assessed ezrin proteolysis. Ethanol permeabilization induced activation of calpainⅠand subsequent proteolysis of ezrin, which resulted in the liberation of ezrin from the apical membrane of the parietal cells. Significantly, expression of calpain-resistant ezrin restored the functional activity of parietal cells in the presence of ethanol.Conclusion: Taken together, our data indicated that ethanol disrupted the apical membrane-cytoskeletal interactions in gastric parietal cells and thereby caused hypochlorhydria.

The average age of the population in many countries is continuing to increase. Older people continue to consume alcohol, often in a binge like fashion. Previous research has demonstrated that older human subjects and aged animal subjects have an increased sensitivity to the effects of ethanol on a variety of behaviors. However, it has yet to be determined if acute ethanol exposure impairs spatial and/or nonspatial memory to a greater extent in aged rats compared to adult rats. In the current studies we trained male rats ranging in age from young adult (2 months of age) to aged rats (29–33 months of age) in the standard nonspatial task followed by the standard spatial task in the Morris water maze. Only animals deemed “cognitively-spared”, that is aged animals that learn as well as young animals, were administered one of two doses of moderate ethanol and had their memory tested 30 min later. Acute ethanol administration produced similar performance impairments in spatial and nonspatial memory in all cognitively-spared animals except for the 29–33 month old animals which showed a significantly greater cognitive impairment in both tasks. In addition, blood ethanol levels were similar across all ages. The present work adds to the growing literature on the selective effects of acute ethanol exposure in aged animals.