Effects Of Acute Ethanol Intake Research Articles

A pre-injury high ethanol intake in rats promotes brain edema following traumatic brain injury

Drinking is a risk factor for traumatic brain injury (TBI), and ethanol can aggravate the outcome by promoting brain edema. The mechanism involved is not fully understood. It has been confirmed that aquaporin-4 (AQP4) and vascular endothelial growth factor (VEGF) play pivotal roles in cytotoxic/vasogenic brain edema individually, and both of these proteins are downstream regulatory factors of hypoxia-inducible factor-1α (HIF-1α). In this study, we used a fluid percussion injury (FPI) model in rats to determine the effects of acute ethanol intake on the expression levels of HIF-1α, AQP4, and VEGF prior to FPI. The animals were sacrificed 1, 2, 3, and 4 days post-injury. We found that the expression levels of HIF-1α and AQP4 were significantly upregulated in the ethanol-pretreated groups, whereas the VEGF expression level was not. In addition, there was a positive correlation between HIF-1α and AQP4. The results of this study indicate that cytotoxic brain edema may play an important role in the early stage of FPI in ethanol-pre-treated animals and that HIF-1α and AQP4 might be involved.

Acute ethanol administration inhibits Toll-like receptor 4 signaling pathway in rat intestinal epithelia

Excess alcohol intake, as in binge drinking, increases susceptibility to microbial pathogens. Alcohol impairs macrophage function by suppression of the Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of acute ethanol intake on the TLR4 pathway in rat intestinal epithelia, which usually encounters luminal antigens at first and participates in the development of intestinal immunity. Twenty Wistar rats were randomly assigned to an ethanol group given ethanol as a 25% (v/v) solution in water at 7.5 g/kg, or a control group given saline, by oral gavage daily for 3 days. The epithelial histology and ultrastructure, the intestinal microflora, peripheral and portal venous plasma lipopolysaccharide (LPS) levels, and somatostatin (SST) levels in the peripheral plasma and small intestine were evaluated. Somatostatin receptor 2 (SSTR2), TLR4, TANK binding kinase-1 (TBK1), activated nuclear factor-κB (NF-κB), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the intestinal mucosa were assayed. LPS responsiveness with or without SST pretreatment was assayed in vitro by quantification of TLR4, TBK1, activated NF-κB, IFN-γ and TNF-α in isolated intestinal epithelia. Mucosal damage was observed in the ethanol group by light and electron microscopy. Escherichia coli cultures were unchanged in rat intestine of the ethanol group compared with controls, but lactobacilli cultures were reduced (p < 0.05). LPS levels increased in peripheral and portal venous plasma (p < 0.05), but mucosal TLR4, TBK1, nuclear NF-κB, IFN-γ and TNF-α were unchanged in the ethanol group. LPS treatment in vitro up-regulated the level of TLR4, TBK1 and nuclear NF-κB as well as the production of IFN-γ and TNF-α in isolated intestinal epithelia in the control (p < 0.05), but not the ethanol group. The stimulatory effects of LPS on intestinal epithelia isolated from the control group were significantly inhibited by SST pretreatment (p < 0.05). The peripheral plasma and intestinal levels of SST and the mucosal expression of SSTR2 in the ethanol group were significantly higher than in the control group (p < 0.05). These findings suggest the hyposensitivity of intestinal epithelial TLR4 to LPS induced by acute alcohol abuse probably through ethanol per se and ethanol-enhanced intestinal mucosal SST pathway may be a novel mechanism for increased susceptibility to intestinal pathogens.

No significant effect of acute moderate alcohol intake on leptin levels in healthy male volunteers

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake in healthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29+/-3.75 years, body mass index (BMI) 24.3+/-3.5, leptin at baseline 3.3+/-3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day 1 of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1,032 g of ethanol (median) consumed within the last 7 days, leptin levels 2.3 mg/ml. A placebo-controlled double-blind trial was performed. Leptin levels of blood samples were taken at baseline (t(1)), before ethanol intake (t(2)), when blood alcohol had reached its maximum (t(3)) and the morning after (t(4)). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) VOLUNTEERS: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t(1)) (rs=0.85, p<0.0001) and follow-up (t(4)) (rs=0.768, p<0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann-Whitney U-test (p=0.669, p=1.0 and p=0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t(1) and t(4) were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.

The effects of acute ethanol intake on isoniazid pharmacokinetics

To assess effects of acute ethanol intake on the pharmacokinetics of isoniazid in healthy male volunteers. Sixteen healthy male, drug-free subjects were studied. Each received in the fasting state, on two occasions separated by at least 1 week, isoniazid (200 mg orally). On one occasion (assigned randomly), subjects received ethanol 0.73 g/kg, 1 h before isoniazid, followed by 0.11 g/kg ethanol orally every hour thereafter for 7 h. Plasma isoniazid and acetylisoniazid concentrations were measured by means of high-performance liquid chromatography. Blood ethanol concentrations were measured hourly by breath analysis. Plasma concentrations of isoniazid and acetylisoniazid were analysed using TOPFIT software. Peak concentrations of isoniazid were reached within 90 min, in both the ethanol-treated and control groups. The ethanol dosage regimen used resulted in peak blood ethanol concentrations between 78 mg/l and 103 mg/l. There was no significant difference in area under the curve, half-life of elimination or the ratio of acetylisoniazid to isoniazid (AcINH/INH) in the sample withdrawn 3 h after isoniazid dose. Acetylator phenotype for patients was the same in both phases, whether assessed by half-life of isoniazid or the AcINH/INH ratio at 3 h. Acute ethanol intake at this dose is unlikely to affect results of acetylation studies in which isoniazid is used as a substrate, whether the half-life of isoniazid or the AcINH /INH ratio at 3 h is used to phenotype patients.

Plasma and Urine Salsolinol in Humans: Effect of Acute Ethanol Intake on the Enantiomeric Composition of Salsolinol

The tetrahydroisoquinoline (TIQ) salsolinol (SAL), a condensation product of dopamine and pyruvate or acetaldehyde, is one of the neuropharmacologically active alkaloids in mammals. Previous HPLC studies have shown that the R-enantiomer of SAL is largely predominant, or is the only enantiomer in the urine of healthy subjects, whereas the S-enantiomer was found predominant in the urine of alcoholics. An enzymatic pathway for SAL formation that is influenced by chronic alcohol intake was proposed. However, our analyses showed that the SAL detectable in human urine and plasma is racemic, at least in healthy subjects. No change of the enantiomeric distribution was observed after an acute alcohol ingestion (1 g alcohol/kg body weight). Using a new method for the resolution of the SAL enantiomers and gas chromatography mass spectrometry analysis, the SAL enantiomers were quantified in the urine and plasma of 24 subjects before and after the intake of alcohol. Special dietary conditions were observed to avoid interferences by the SAL of the foodstuff. Although the distribution of SAL enantiomers was not changed after alcohol intake, the total urinary SAL output and the plasma concentration of SAL were significantly influenced in different ways. Only five subjects showed a significant increase both in plasma SAL concentration and in the total urinary SAL output, whereas 19 subjects showed decreased or unchanged SAL levels after alcohol administration. Data also show that only the subjects with low baseline levels (mean of 0.148 ng SAL/ml plasma) tend to increase SAL levels after ethanol ingestion, which may imply some genetic basis for the response.

Inhibition of testosterone synthesis by ethanol: Role of luteinizing hormone

The effects of acute ethanol intake (1.5 g/kg) on plasma testosterone and luteinizing hormone (LH) concentrations were examined in male Long-Evans rats. Ethanol decreased the serum LH concentrations by 21% and 42% 30 and 60 minutes after ethanol administration respectively. The testosterone concentrations decreased later (30 min: +8%; 60 min; −30%). The LH concentrations were highly correlated with subsequent (60 min later) testosterone concentrations (LH 30min: r = .688, p<0.001, n = 25; LH 60 min: r = .678, p<0.001), but less so with concurrent testosterone concentrations (30 min: r = .187, N.S.; 60 min: r = .552, p<0.004). To further test the influence of LH, naloxone (11 mg/kg) was administered, which elevated the LH levels within 30 min by 103% in controls. Naloxone also increased serum LH concentration by 34% in ethanol-treated rats at 30 min, but these animals nevertheless had lower ( p<0.01) testosterone levels at 60 min than did control animals without naloxone and ethanol treatment. It is concluded that although ethanol-induced changes in serum LH levels may play a role in the decrease of serum testosterone concentrations in rats, there are also other mechanisms by which ethanol may produce these effects.

Effect of Acute Ethanol Intake and Hangover on the Levels of Plasma and Urinary Catecholamines and Lymphocytic β‐Adrenergic Receptors

To determine whether acute ethanol administration affects the function of the adrenergic system the concentrations of plasma catecholamines and cyclic AMP (cAMP), the level of lymphocytic beta-receptors, the concentration of basal and isoproterenol-stimulated lymphocytic cAMP and the excretion of urinary catecholamine metabolites were studied in six healthy men. These parameters were also measured during the hangover, both under resting condition and during an anaerobic ergometer exercise. Acute intake of ethanol (1.5 g/kg body weight) had no statistically significant effect either on plasma adrenaline and noradrenaline concentrations or beta-adrenergic receptor levels. Ethanol consumption did neither change the urinary excretion of catecholamine metabolites (homovanillic acid, normetanephrine, metanephrine, and 3-methoxyhydroxymandelic acid). Exercise was associated with a 6-10-fold elevation in plasma adrenaline and noradrenaline concentrations and with a two- to threefold elevation on beta-adrenergic receptor levels. This effect of exercise was not modified by preceding alcohol intake and resulting hangover. These preliminary findings suggest that acute alcohol intake does not significantly alter the concentration and functioning of human beta-adrenergic receptors.

Effect of acute ethanol intake on thromboxane and prostacyclin in human

To investigate the effects of acute ethanol administration on the production of proaggregatory thromboxane A 2 (TxA 2) and anti-aggregatory prostacyclin (PGI 2), ethanol (1.5 g/kilogram body weight) was given to eight healthy nonsmoking men, and the stable metabolites thromboxane B 2 (TxB 2) and 6-keto-prostaglandin F 1α (6-keto-PGF 1α), respectively, measured by radioimmunoassay from serial blood samples before drinking and during the ensuing 18 hours. Each subject was studied as his own control on another occasion when only an equivalent volume of water was given. Serum TxB 2 level decreased (p < 0.01) from 206 + 31 ng/ml ( mean) ± S.E. to 167 2 ± 24 and 161 ± 23 ng/ml (two and four hours after beginning of the drinking, respectively) concomitantly with the attainment of maximal blood ethanol concentrations (about 120 mg/100 ml), whereas no changes occurred in plasma 6-keto-PGF 1α concentrations. Our results may provide an explanation for known effects of ethanol on platelet aggregation. They also raise speculation whether TxA 2-inhibition and the antiatherogenic effect of alcohol intake are somehow related.

Effect of acute ethanol intake on plasma 11 hydroxycorticosteroid levels

In this study it has been shown that in normal subjects the oral intake of alcohol in doses leading to a moderate degree of intoxication results in increased plasma 11 hydroxycorticoid (11-OHCS) levels. The plasma 11-OHCS levels were significantly increased after the oral administration of alcohol, 1.5 ml./Kg. weight, in a 20% solution in water. In similar control experiments, no increase in 11-OHCS release was noted. This increase is thought to be due to stimulation of adrenocortical function. In light of these findings, the effect of repeated and prolonged alcohol intake on the adrenocortical activity is felt to be a problem which merits further study.