Acute Ethanol Ingestion Research Articles

Apoptosis Due to After-effects of Acute Ethanol Exposure in Brain Cortex: Intrinsic and Extrinsic Signaling Pathways

Alcohol hangover is the combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration approaches zero. We previously demonstrated that hangover provokes mitochondrial dysfunction, oxidative stress, imbalance in antioxidant defenses, and impairment in cellular bioenergetics. Chronic and acute ethanol intake induces neuroapoptosis but there are no studies which evaluated apoptosis at alcohol hangover. The aim of the present work was to study alcohol residual effects on intrinsic and extrinsic apoptotic signaling pathways in mice brain cortex. Male Swiss mice received i.p. injection of ethanol (3.8 g/kg) or saline. Six hours after injection, at alcohol hangover onset, mitochondria and tissue lysates were obtained from brain cortex. Results indicated that during alcohol hangover a loss of granularity of mitochondria and a strong increment in mitochondrial permeability were observed, indicating the occurrence of swelling.Alcohol-treated mice showed a significant 35% increase in Bax/Bcl-2 ratio and a 5-fold increase in the ratio level of cytochrome c between mitochondria and cytosol. Caspase 3, 8 and 9 protein expressions were 32%, 33% and 20% respectively enhanced and the activity of caspase 3 and 6 was 30% and 20% increased also due to the hangover condition. Moreover, 38% and 32% increments were found in PARP1 and p53 protein expression respectively and on the contrary, SIRT-1 was almost 50% lower than controls due to the hangover condition. The present work demonstrates that alcohol after-effects could result in the activation of mitochondrial and non-mitochondrial apoptosis pathways.

Risk assessment of low-dose ethanol in food.

A high variety of food contains low doses of ethanol which are sometimes difficult to identify by consumers (adults or children). However, even low doses of ethanol intake raises several toxicological concerns. In the present study, an enzymatic assay and an HS-GC/MS procedure were applied to determine the ethanol levels of 1260 samples from different food categories covering "nonalcoholic" beer, fruit juices/drinks, baked goods, bananas and baby foods. Based on these results, ethanol levels resulting from acute or chronic ethanol intake was calculated using consumption data from the EFSA Comprehensive European Food Consumption Database. Thus, health-based guidance values (HBGV) for ethanol intake were derived for acute or chronic exposure based on the available literature. For acute exposure, very few samples resulted in concerning ethanol uptake levels but following chronic exposure the here derived HBGV level was exceeded in several cases. This is mainly due to the following reasons: (1) certain amounts of ethanol are still tolerated in "nonalcoholic" beer and (2) presence of endogenous produced ethanol in bananas or baked goods via fermentation. Most analysed food samples, however, do not result in elevated ethanol doses linked with a potentially high risk following acute and chronic consumption by adults and children.

Alcohol-associated capillarization of sinusoids: A critique since the discovery by Schaffner and Popper in 1963.

This article reviews the literature on capillarization of hepatic sinusoids since its discovery in 1963. Liver sinusoidal endothelial cells are uniquely fenestrated and lack an underlying basement membrane. In chronic liver disease, the sinusoids capillarize and transform into systemic capillaries, a process termed capillarization of sinusoids. The histopathology is marked by defenestration, basement membrane formation, and space of Disse fibrogenesis. Capillarized sinusoids compromise the bidirectional exchange of materials between sinusoids and hepatocytes, leading to hepatocellular dysfunction. Sinusoidal capillarization was first described in active cirrhosis of alcoholics in 1963. Since then, it has been found in early and progressive stages of alcoholic hepatic fibrosis before the onset of cirrhosis. The sinusoidal structure is not altered in alcoholic steatosis without fibrosis. Defenestration impairs the ability of the endothelium to filter chylomicron remnants from sinusoids into the Disse's space, contributing to alcohol-induced postprandial hyperlipidemia and possibly atherosclerosis. Ethanol also modulates the fenestration dynamics in animals. In baboons, chronic alcohol consumption diminishes endothelial porosity in concomitance with hepatic fibrogenesis and in rats defenestrates the endothelium in the absence of fibrosis, and sometimes capillarizes the sinusoids. Acute ethanol ingestion enlarges fenestrations in rats and contracts fenestrations in rabbits. In sinusoidal endothelial cell culture, ethanol elicits fenestration dilation, which is likely related to its interaction with fenestration-associated cytoskeleton. Ethanol potentiates sinusoidal injury caused by cocaine, acetaminophen or lipopolysaccharide in mice and rats. Understanding ethanol's mechanisms on pathogenesis of sinusoidal capillarization and fenestration dynamics will lead to development of methods to prevent risks for atherosclerosis in alcoholism.

Impact of acute ethanol intake on cardiac autonomic regulation

Acute alcohol consumption may facilitate cardiac arrhythmias underlying the ‘Holiday Heart Syndrome’. Autonomic imbalance is promoting atrial arrhythmias. We analyzed the effects of alcohol on measures of the cardiac autonomic nervous system and their relation to arrhythmias. In 15 healthy individuals, alcohol was administered parenterally until a breath alcohol concentration of 0.50 mg/l. High-resolution digital 30-min ECGs were recorded at baseline, at the time of maximum alcohol concentration, and after alcohol concentration returned to near baseline. Using customized software, we assessed periodic repolarization dynamics (PRD), deceleration capacity (DC), standard measures of heart rate variability (SDNN; RMSSD; LF; HF), and standard ECG parameters (mean heart rate; PQ; QRS; QTc interval). At the maximum alcohol concentration, PRD levels were significantly increased compared to baseline [1.92 (IQR 1.14–3.33) deg2 vs. 0.85 (0.69–1.48) deg2; p = 0.001]. PRD levels remained slightly increased when alcohol concentrations returned to baseline. DC levels were significantly decreased at the maximum alcohol concentration compared to baseline [7.79 (5.89–9.62) ms vs. 9.97 (8.20–10.99) ms; p = 0.030], and returned to baseline levels upon reaching baseline levels of alcohol. Standard HRV measures were reduced at maximum alcohol concentration. The mean heart rate increased significantly during alcohol administration. QRS and QTc duration were significantly prolonged, whereas PQ interval showed no change. Our findings revealed an increase of sympathetic activity and a reduction of parasympathetic activity under the influence of alcohol administration, resulting in autonomic imbalance. This imbalance might ultimately trigger arrhythmias underlying the ‘Holiday Heart Syndrome’.

Abstract 13050: Acute Alcohol-Induced Enhanced Cardiac Depression in a Canine Model of Chronic Alcohol Consumption: Adverse Effects on Left Ventricle and Myocyte Contraction, [Ca 2+ ] i Transient and Ca 2+ Current

Background: Acute alcohol ingestion produces transient RAS activation. Alcoholics have an enhanced RAS activation after acute ethanol ingestion. Thus, chronic alcohol users may have enhanced cardiac functional responses to acute alcohol intake. However, it is unclear whether and how chronic alcohol intake alters cardiac response to acute alcohol exposure. We tested the hypothesis that acute alcohol may exacerbate cardiac depression and [Ca 2- ] i dysregulation, thus play important role in development of irreversible cardiomyopathy in alcoholics. Methods: We compared LV and cardiomyocyte response to acute alcohol in 6 chronically-instrumented conscious dogs before and 6 months after the once daily ingestion of alcohol (400 ml, 22% providing 33% of total daily caloric intake). Results: In conscious dogs, 6 months of alcohol significantly decreased LV contractility by 48% measured by the slopes of pressure-volume relations (E ES , 48%, 4.4 vs 8.4 mmHg/ml and M SW , 50.8 vs 98.6 mmHg) and increased the time constant of relaxation (τ, 78%, 47.8 vs 26.9 ms). In the alcoholic animals, when compared with the same animals prior to alcohol, acute alcohol (0.2 g/kg, iv, plasma level 62.3 ± 8 mg/dL) caused a greater decrease in LV contractility (47% vs 23%) and increase in τ (27% vs11%). In isolated myocytes, abrupt exposure to alcohol (250 mM) produced significant decreases in cell contraction, [Ca 2+ ] i transient ([Ca 2+ ] i ) and Ca 2+ current (I Ca,L ) in both normal and alcoholic myocytes. However, compared with the isolated cells obtained from LV biopsied tissues of the same animals prior to alcohol, the acute alcohol-induced decrease in I Ca,L (alcoholic: 50%, 1.3 vs 2.6; normal: 29%, 4.0 vs 5.6 pA/pF) was much greater in the alcoholic myocytes, the resulting reductions in the cell contractility, dL/dtmax (alcoholic: 46%, 36vs67; normal: 24%, 82vs108 μm/s), the percent shortening (49% vs 24%) and relengthening, dR/dtmax were doubled. Conclusion: In chronically alcohol-fed dogs, acute alcohol produces increased direct inhibition in LV and myocyte contractility, relaxation and exacerbates [Ca 2+ ] i hemostasis. The chronic alcohol-induced increased cardiac sensitivity to acute alcohol may play an important role in the functional impairment in alcoholic cardiomyopathy.

Acute Effects of Ethanol on Hippocampal Spatial Representation and Offline Reactivation.

Acute alcohol exposure impairs hippocampus-dependent spatial memory. However, there is little evidence for the effects of ethanol on the spike patterns of hippocampal cell populations. Here, we examined how the spatial firing patterns of place cells, neurons that encode specific locations, were altered in rats that were intraperitoneally injected with 1.5 g/kg ethanol. Ethanol administration partly reduced or abolished place-selective spiking of a subset of place cells during running periods in a spatial task, whereas a subset of place fields newly emerged, suggesting a partial reorganization of hippocampal spatial maps by ethanol. On the other hand, ethanol administration did not significantly alter the frequency of hippocampal sharp-wave ripple (SWRs) and synchronous spike patterns during resting periods, suggesting that offline memory consolidation and retrieval mechanisms underpinned by hippocampal neuronal synchronization are not strongly affected by ethanol. These results indicate that acute ethanol intake mainly affects the encoding of external information but has little impact on internal memory processing.

Kissorphin improves spatial memory and cognitive flexibility impairment induced by ethanol treatment in the Barnes maze task in rats.

Acute and chronic ethanol intake, as well as ethanol withdrawal, exert learning disabilities. Of all the neurotransmitters in the brain, endogenous opioid peptides are thought to participate in ethanol effects. Kisspeptins, including kisspeptin-10, are peptides produced in the part of brain involved in the consolidation of memory and orientation. A new derivative of kisspeptin-10 is kissorphin (Tyr-Asn-Trp-Asn-Ser-Phe-NH2), a peptide with anti-opioid-activity. Hence, the aim of our study was to reveal whether kissorphin (1, 3, and 10 nmol, i.v.) was able to prevent or reverse learning deficits such as spatial memory retention and reversal learning induced by acute ethanol administration (1 × 1.75 g/kg., i.p.) and reversal learning induced by ethanol withdrawal (11-13 days from 'binge-like' ethanol input-5.0 g/kg, i.g. for 5 days) in the Barnes maze task in rats. Our study demonstrated that acute kissorphin administration prevented spatial memory (higher doses) impairments and attenuated reversal learning deficits induced by acute ethanol administration, although the reversal learning impairment may have been due to spatial learning impairments rather than cognitive flexibility impairments. Moreover, kissorphin given prior to first reversal learning trial for 3 consecutive days in the Barnes maze task during withdrawal from 'binge-like' ethanol administration, significantly attenuated cognitive flexibility impairment in the ethanol-withdrawal rats. In the acute and chronic ethanol experiments, kissorphin was the most effective at the dose of 10 nmol. In conclusion, the ethanol-induced spatial memory impairment may be reversed by pharmacological manipulation of the endogenous opioid system.

Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice.

Excessive alcohol consumption is associated with spontaneous burning pain, hyperalgesia, and allodynia. Although acetaldehyde has been implicated in the painful alcoholic neuropathy, the mechanism by which the ethanol metabolite causes pain symptoms is unknown. Acute ethanol ingestion caused delayed mechanical allodynia in mice. Inhibition of alcohol dehydrogenase (ADH) or deletion of transient receptor potential ankyrin 1 (TRPA1), a sensor for oxidative and carbonyl stress, prevented allodynia. Acetaldehyde generated by ADH in both liver and Schwann cells surrounding nociceptors was required for TRPA1-induced mechanical allodynia. Plp1-Cre Trpa1fl/fl mice with a tamoxifen-inducible specific deletion of TRPA1 in Schwann cells revealed that channel activation by acetaldehyde in these cells initiates a NADPH oxidase-1-dependent (NOX1-dependent) production of hydrogen peroxide (H2O2) and 4-hydroxynonenal (4-HNE), which sustains allodynia by paracrine targeting of nociceptor TRPA1. Chronic ethanol ingestion caused prolonged mechanical allodynia and loss of intraepidermal small nerve fibers in WT mice. While Trpa1-/- or Plp1-Cre Trpa1fl/fl mice did not develop mechanical allodynia, they did not show any protection from the small-fiber neuropathy. Human Schwann cells express ADH/TRPA1/NOX1 and recapitulate the proalgesic functions of mouse Schwann cells. TRPA1 antagonists might attenuate some symptoms of alcohol-related pain.

Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency

Aldehyde dehydrogenase 2 (ALDH2) deficiency causes “Asian flush syndrome,” presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%–40% of East Asians and 8% of the world population. ALDH2 is the key enzyme in ethanol metabolism; with ethanol challenge, the common ALDH2*2 (E487K) mutation results in accumulation of toxic acetaldehyde. ALDH2*2 heterozygotes have increased risk for upper digestive tract cancers, compounded by smoking and drinking alcohol. We hypothesized that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) would correct the deficiency state. AAVrh.10hALDH2 was administered intravenously to Aldh2 knockout (Aldh2−/−) and Aldh2 E487K knockin homozygous (Aldh2E487K+/+) mice. Following acute ethanol ingestion, untreated ALDH2-deficient mice had elevated acetaldehyde levels and performed poorly in behavioral tests. In contrast, treated Aldh2−/− and Aldh2E487K+/+ mice had lower serum acetaldehyde levels and improved behavior. Thus, in vivo AAV-mediated ALDH2 therapy may reverse the deficiency state in ALDH2*2 individuals, eliminating the Asian flush syndrome and reducing the risk for associated disorders.

2477-PUB: Blood Beta Hydroxybutyrate Levels in Adult Patients Presenting to Emergency Department

Ketone bodies are an important alternate fuel source with fasting. Our aim was to describe point of care blood beta hydroxybutyrate (BHB) in patients presenting to emergency (ED). We performed a retrospective study. The population consisted of adult patients attending emergency department of a tertiary referral hospital who had a BHB measurement and venous blood gas measurement (VBG) performed at presentation to ED. Between March-September 2018 inclusive, 4356 patients had at least one VBG performed, and of these 842 patients had at least one BHB level performed whilst in ED. Of the whole cohort, 604 patients were admitted and 238 discharged from ED or short stay ward. Results are shown as mean±SD (range). Age was 62.5±21.6 years (16.1-102.5). 55% of cohort were male. Length of stay was 6.23±9.99 days (0.35-77.77), and Charlson score 1.91±2.03 (0-15). Blood glucose (BG) was 10.5 ±7.3mmol/L (2-54mmol/L), lactate 2.2±1.7mmol/L (0.3-21), and BHB 0.6±1.2mmol/L (0-8.4). Of the whole cohort, 404 patients had diabetes. Excluded from subsequent analysis were 18 cases of diabetic ketoacidosis and 6 cases of hyperosmotic hyperglycaemic syndrome. Of this cohort, BHB level did not differ according to diabetes status (0.52±0.9mmol/L those with diabetes versus 0.41±0.75mmol/L in those without) yet BG (13.7±7.4mmol/L versus 6.8±2.8mmol/L, p<0.01) was higher as was lactate (2.3±1.6mmol/L versus 2.1±1.8mmol/L, p<0.05). Where acute vomiting was documented to be present versus not recorded, BHB was higher (0.64±1.0 mmol/L versus 0.43±0.81mmol/L). Where acute ethanol intake was documented, BHB was not significantly higher (0.66±1.34mmol/L versus 0.44±0.79mmol/L). BHB ≥3mmol/L was seen in 2.9% of those with diabetes and 2.1% of those without diabetes. Although serum albumin was no different, BMI was lower in those with BHB ≥ 3mmol/L (23.5±7.7kg/m2 versus 27.6±6.9kg/m2). Ketosis is commonly seen in ED, is associated with reduced oral intake and is not confined to those with diabetes. Disclosure B. Depczynski: None. A.T. Lee: None. W.F. Varndell: None. A.L. Chiew: None.

Perivascular adipose tissue protects against the vascular dysfunction induced by acute ethanol intake: Role of hydrogen peroxide

AimWe investigated the consequences of acute ethanol intake on the anti-contractile effect of perivascular adipose tissue (PVAT). MethodsThe effects of a single dose of ethanol (1 g/kg; p.o. gavage) on the vascular function were assessed within 30 min in male Wistar rats. ResultsEthanol decreased the relaxation induced by acetylcholine and increased the contraction induced by phenylephrine in endothelium-intact, but not in endothelium-denuded aortas without PVAT. The vascular dysfunction induced by ethanol was not observed in aortic rings with PVAT. Nω-Nitro-l-arginine methyl ester (L-NAME), NG-nitro-l-arginine (L-NNA) and 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not tiron or tempol, increased the contraction induced by phenylephrine in endothelium-intact aortas with PVAT from control and ethanol-treated rats. Catalase increased phenylephrine-induced contraction in aortas with PVAT from ethanol-treated rats, but not from control rats. Conversely, inhibition of catalase with aminotriazole decreased phenylephrine-induced contraction in aortas from ethanol-treated rats. Treatment with ethanol increased hydrogen peroxide (H2O2) levels and decreased catalase activity in aortas with PVAT. Ethanol increased superoxide anion (O2−) generation in aortas with or without PVAT. Superoxide dismutase (SOD) activity was not affected by ethanol intake. In situ quantification of H2O2 using 2′7′dichlorodihydrofluorescein diacetate (DCFH-DA) revealed increased levels of H2O2 in periaortic PVAT from ethanol-treated rats. However, in situ evaluation of nitric oxide (NO) in both aorta and PVAT showed no differences between groups. ConclusionsOur study provides novel evidence that the periaortic PVAT protects against the vascular dysfunction induced by acute ethanol intake through a mechanism that involves increased generation of H2O2.

No blue-yellow color vision impairment after acute ethanol ingestion.

Several studies showed that chronic ethanol exposure can cause color vision deficiencies. There has been no agreement about the axis of color defects due to alcohol misuse since changes in the red-green and the blue-yellow axis have been described in literature. The acute influence of alcohol on the blue-yellow color vision has not been studied as well. The aim of this study was to determine the effect of acute alcohol ingestion on blue-yellow color vision by using short wavelength automated perimetry (SWAP) and anomaloscopy with the Moreland equation. This is the first study evaluating that question by using SWAP and anomaloscopy. Sixteen healthy subjects without a history of alcohol-related and ophthalmological problems were examined by SWAP and anomaloscopy (Moreland equation) before and after alcohol ingestion. Mean sensitivity (MS), mean deviation (MD), loss of variance (LV), reliability factor (RF), and duration of examination were assessed for perimetry and match midpoint (MP), matching range (MR), and duration of examination for anomaloscopy. Blood alcohol concentrations (BAC) were determined by gas chromatography and phosphatidylethanol concentrations (marker of an alcohol misuse) by liquid-chromatography tandem-mass spectrometry in venous blood samples from a cubital vein. Mean blood BAC was 0.86±0.20g/kg while performing perimetry and 0.84±0.20g/kg while performing anomaloscopy (BAC: 0.1g/kg≈0.01g/dL). MS, MD, RF, MP, MR, and duration of perimetry examination were not altered significantly after alcohol intake. LV showed a significant increase. The duration of anomaloscope testing was shortened significantly under the influence of alcohol. The subjects also revealed a significantly narrower matching range after alcohol intake. In the range of 0.8g/kg BAC, no blue-yellow vision deficiencies could be demonstrated. In further studies, the effect of higher BAC on blue-yellow vision should be investigated by different methods.

Spontaneously hypertensive rats exhibit higher sensitivity to ethanol-induced hypotensive effects: Role of NMDA receptors and nitric oxide in rostral ventrolateral medulla.

Intake of ethanol (alcohol) affects cardiovascular function. Acute ethanol intake has been shown to lower blood pressure (BP) in hypertensive patients. The present study was undertaken to examine the effects and mechanisms of acute administration of ethanol on BP in hypertensive and normotensive rats. Ethanol was given by intraperitoneal (i.p.) injection in male spontaneously hypertensive rats (SHRs) and the normotensive Wistar-Kyoto rats (WKYs). BP responses were measured in free-moving conscious rats or in urethane-anesthetized rats. Inhibitors were applied by bilateral microinjection into the rostral ventrolateral medulla (RVLM). Nitric oxide (NO•) levels and glutamate levels were determined by nitrate and nitrite (NOx) analyzer and HPLC-ECD, respectively. Intraperitoneal (i.p.) injection of ethanol (1.6g/kg) caused a significant decrease in BP in free-moving or in anesthetized SHRs but not in WKYs. A higher dose (3.2g/kg) of ethanol decreased BP in both SHRs and WKYs, although the depressor responses in SHRs occurred significantly earlier than those in WKYs. The blood ethanol concentrations 60min after injection were similar in SHRs and WKYs. Bilateral microinjection of nitric oxide synthase (NOS) inhibitors or glutamatergic NMDA receptor antagonists into the RVLM 5min after administration of ethanol significantly inhibited the ethanol-induced depressor effects in SHRs. The levels of NOx and glutamate release in the RVLM following ethanol administration and the NOx content in the RVLM areas 30min after administration were significantly increased in SHRs, but not in WKYs. Our results showed that SHRs were more sensitive to ethanol-induced hypotensive effects than WKYs because of augmentation of ethanol-induced expression of the glutamatergic NMDA receptor/NO• signal in the RVLM of SHRs.

Effect of autophagy inhibitor chloroquine on acute alcoholinduced liver disease

To investigate the role of autophagy inhibitor chloroquine (CQ) in acute ethanol-induced liver injury and its mechenism. Twenty-one C57BL/6 male mice were randomly divided into three groups:control group, ethanol group, CQ + ethanol group (n=7). Mice in ethanol group were administered 33% (v/v) ethanol at a dose of 4.5 g/kg body weight. Ethanol-induced liver steatosis in each group was detected by hematoxylin and eosin staining. Hepatic lipid accumulation was detected by staining with Oil red O. Hepatic tissue triglyceride (TG) levels, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were determined by biochemical assays. Protein expression of microtubule-associated protein 1 light chain 3(LC3) and nuclear factorκB p65(NF-κB p65) were measured by Western blot and immunofluorescence. Pro-inflammatory factors tumor necrosis factor-α(TNF-α)、interleukin 6(IL-6) were detected by ELISA. Compared with control group, ethanol induced liver injury proved by accumulation of hepatic lipids, TG levels, AST and ALT activities were significantly increased by ethanol, protein expression of LC3-Ⅱ was also markedly increased by ethanol. Compared with ethanol group, addition of CQ increased furtherthe level of LC3-Ⅱexpression, and TG amount, serum AST and ALT activities, and the expression of NF-κB p65, TNF-αand IL-6. Acute ethanol-intake could induce liver steatosis and inflammation, and autophagy inhibitor CQ exacerbatedethanol-induced liver injury, suggested that autophagy might be protective effect in acute ethanol-induced liver disease.

Forced ethanol ingestion by Wistar rats from a juvenile age increased voluntary alcohol consumption in adulthood, with the involvement of orexin-A.

Human adolescents who drink alcohol are more likely to become alcoholics in adulthood. Alcohol administration (intraperitoneally) or drinking (in a 2-bottle free choice paradigm) during the juvenile/adolescent age of rats promotes voluntary alcohol consumption in adulthood. On the other hand, there is growing evidence that the orexinergic system plays a role in several rewarded behaviors, including alcohol ingestion. Since it is unknown what effect is exerted in adulthood by forced oral ethanol intake and/or administration of orexin-A (OX-A) in juvenile rats, the present study aimed to evaluate this question. A group of male Wistar rats was forced to drink ethanol (10% v/v) as the only liquid in the diet from weaning (postnatal day 21) to postnatal day 67 (46 days), followed by a forced withdrawal period. An age-matched group was raised drinking tap water (control). OX-A or its vehicle was microinjected intracerebroventricularly (i.c.v.) (1nmol/0.6μL) to explore its effect as well. Locomotor activity and voluntary ethanol consumption were later assessed in all groups. The rats forced to consume ethanol early in life showed an elevated level of ambulation and alcohol ingestion in adulthood. A single injection of OX-A increased locomotor activity and acute ethanol intake in rats with or without prior exposure to alcohol at the juvenile stage. In conclusion, forced ethanol consumption in juvenile rats led to increased voluntary alcohol drinking behavior during adulthood, an effect likely facilitated by OX-A.

Acute ethanol and taurine intake affect absolute alpha power in frontal cortex before and after exercise.

Taurine and alcohol has been popularly ingested through energy drinks. Reports from both compounds shows they are active on nervous system but little is known about the acute effect of these substances on the frontal cortex in an exercise approach. The aim of this study was to determine the effects of 0,6mldL-1 of ethanol (ET), 6g of taurine (TA), and taurine with ethanol (TA+ET) intake on absolute alpha power (AAP) in the frontal region, before and after exercise. Nine participants were recruited, five women (22±3years) and four men (26±5years), for a counterbalanced experimental design. For each treatment, the tests were performed considering three moments: "baseline", "peak" and "post-exercise". In the placebo treatment (PL), the frontal areas showed AAP decrease at the post-exercise. However, in the TA, AAP decreased at peak and increased at post-exercise. In the ET treatment, AAP increased at the peak moment for the left frontal electrodes. In the TA+ET treatment, an AAP increase was observed at peak, and it continued after exercise ended. These substances were able to produce electrocortical activity changes in the frontal regions after a short duration and low intensity exercise. Left and right regions showed different AAP dynamics during peak and post-exercise moments when treatments were compared.

Hung over? Maybe it's your overactive microglia.

Acute ethanol intake is associated with a mild suppression of microglial activity followed by a more robust inflammatory reaction during the withdrawal period.

Oral glutamate intake reduces acute and chronic effects of ethanol in rodents

Purpose: To assess the effects of oral glutamate intake on acute motor effects and chronic intake of ethanol in rodents. Methods : The acute effects of ethanol on motor function were studied in ICR mice by giving 2 or 6 g/kg of ethanol 2 h after distilled water or 2.5 g/kg glutamate per os. Thirty minutes after ethanol treatment, behavioral assays, including rotarod tests and foot print analysis were monitored. In chronic ethanol treatment, male Wistar rats were trained to consume ethanol-sucrose solution during a 2-h period daily, starting with 2 % ethanol/10 % sucrose and gradually increasing to 10 % ethanol/5 % sucrose solution over 56 days. After training session, the drug treatment phase was done for 10 days. The animals were force-fed 50 mg/kg/day topiramate or 2.5 g/kg/day glutamate 2 h before ethanol treatment sessions. Each day, ethanol intake, water intake, food intake and body weight were recorded. Results : Mice that received 2 or 6 g/kg of ethanol orally, showed a significant reduction in time on the rod in the rotarod test and a significant increase in both forelimb and hindlimb stride lengths when compared to control. Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of ethanol. In chronic ethanol treatment, the intake of 10 % ethanol/5 % sucrose, accessible for 2 h, was significantly decreased in rats treated with either topiramate or glutamate. Conclusion : These results provide evidence that oral glutamate administration help to reduce the acute motor effects of ethanol in mice and ethanol intake in the chronic ethanol drinking rats. Keywords : Ethanol, Glutamate, Motor functions, Ethanol intake, Rodents

Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

BackgroundThe mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted.ObjectiveTo investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation.MethodsMale Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration.ResultsVitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB.ConclusionAcute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism.

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells.

Increases in pro-inflammatory cytokine levels and tissue-infiltrating leukocytes have been closely linked to increased systemic and local inflammation, which result in organ injury. Previously, we demonstrated the beneficial and hepatoprotective anti-inflammatory effects of acute ethanol (EtOH) ingestion in an in vivo model of acute inflammation. Due to its undesirable side-effects, however, EtOH does not represent a therapeutic option for treatment of acute inflammation. Therefore, in this study, we compared the effects of acute EtOH exposure with ethyl pyruvate (EtP) as an alternative anti-inflammatory drug in an in vitro model of hepatic and pulmonary inflammation. Human hepatocellular carcinoma cells Huh7 and alveolar epithelial cells A549 were stimulated with either interleukin (IL) IL-1β (1 ng/ml, 24 h) or tumor necrosis factor (TNF) (10 ng/ml, 4 h), and then treated with EtP (2.5-10 mM), sodium pyruvate (NaP, 10 mM) or EtOH (85-170 mM) for 1 h. IL-6 or IL-8 release from Huh7 or A549 cells, respectively, was measured by an enzyme‑linked immunosorbent assay. Neutrophil adhesion to cell monolayers and CD54 expression were also analyzed. Bcl-2 and Bax gene expression was determined by RT-qPCR, and western blot analysis was performed to determine the mechanisms involved. Treating A549 cells with either EtOH or EtP significantly reduced the IL-1β- or TNF‑induced IL-8 release, whereas treating Huh7 cells did not significantly alter IL-6 release. Similarly, neutrophil adhesion to stimulated A549 cells was significantly reduced by EtOH or EtP, whereas for Huh7 cells the tendency for reduced neutrophil adhesion rates by EtOH or EtP was not significant. CD54 expression was noticeably reduced in A549 cells, but this was not the case in Huh7 cells after treatment. The Bax/Bcl-2 ratio was dose‑dependently decreased by EtOH and by high-dose EtP in A549 cells, indicating a reduction in apoptosis, whereas this effect was not observed in Huh7 cells. The underlying mechanisms involve reduced phosphorylation of Akt and nuclear factor-κB (NF-κB) p65. We noted that as with EtP, EtOH reduced the inflammatory response in lung epithelial cells under acute inflammatory conditions. However, due to the low impact which EtP and EtOH had on the hepatocellular cells, our data suggest that both substances exerted different effects depending on the cellular entity. The possible underlying mechanisms involved the downregulation of Akt and the transcription factor NF-κB, but further research on this subject is required.