Blood Acetaldehyde Concentrations Research Articles

Effect of alcohol dehydrogenase-1B and -7 polymorphisms on blood ethanol and acetaldehyde concentrations in healthy subjects with a history of moderate alcohol consumption.

This study aims to evaluate the effect of ADH1B and ADH7 genotypes on blood acetaldehyde and ethanol levels after alcohol ingestion, and to measure the genotoxic effect of smoking and ethanol on the buccal cells, also controlling for ADH variants. We recruited healthy Italian subjects with at least a moderate history of alcohol consumption. All subjects were given an alcoholic drink of 0.4 g ethanol /kg of body weight. Blood venous samples were collected at baseline, and 30, 60, 90, and 120 minutes after ingestion. Buccal cells were collected before ethanol ingestion. Sixty subjects were enrolled in the study. Individuals with the ADH1B GG genotype had median ethanol levels of 5.0mM (IQR 3.4-7.2), and those with the ADH1B GT/TT genotype had 4.7mM (IQR 4.2-4.8). Corresponding acetaldehyde levels were 1.5μM (IQR 0.7-2.6) for ADH1B GG genotype and 1.6μM (IQR 1.5-1.7) for ADH1B CG/GG genotype. Individuals with the ADH7 CC genotype had median ethanol levels of 5.0mM (IQR 3.3-7.2), while 5.0mM (IQR 4.7-5.6) was in those with the ADH7 CG/GG genotype. Corresponding acetaldehyde levels were 1.5 μM (IQR 0.7-2.6) for ADH7 CC genotype and 1.5 μM (IQR 1.4-1.6) for ADH7 CG/GG genotypes. A non-significant increase in the frequency of karyolitic and pyknotic cells was found in the group of heavy drinkers and current smokers, when compared to the moderate drinkers and the non-smokers. Our study does not support the hypothesis that ADH1B and ADH7 genotypes affect blood ethanol and acetaldehyde concentration.

Establishment of a BALB/c Mouse Model for Assessing the Degree of Inebriation Induced by Luzhou-Flavor Liquors.

This investigation was carried out to determine the differences in the degree of inebriation induced by Luzhou-flavor liquors having the same ethanol content. A BALB/c mouse model was used to test the effects of two liquors on the loss of the righting reflex (LORR) and the duration (DUR) of the LORR, as indices of the degree of inebriation. The blood ethanol concentration, blood acetaldehyde concentration, acetylcholinesterase activity in the hippocampus, and concentrations of dopamine and serotonin in the striatum were also determined. The degrees of inebriation induced by the two liquors were 0.694 and 0.404, as quantified by LORR and LORR DUR. The liquor that induced the lower degree of inebriation also induced lower blood ethanol and blood acetaldehyde concentrations. Moreover, it had no significant effects on acetylcholinesterase activity in the hippocampus or on the concentrations of dopamine or serotonin in the striatum. Chinese liquors with the same ethanol content can be distinguished by the degree of inebriation they induce. A relationship was found between the internal composition of the liquor and the degree of inebriation it induced. Our data support choosing liquors with low degrees of inebriation to reduce their harmful effects.

Influence of Tiopronin on the Metabolism of Alcohol in Healthy Subjects.

Drug safety- and drug-alcohol interaction studies have mainly been conducted for frequently prescribed drugs with high financial interests. Orphan drugs such as tiopronin (ORPHA25073) are often neglected in terms of clinical research. Tiopronin is a drug that is mainly used for the treatment of cystinuria. In this study, the interaction of tiopronin regarding the metabolism of alcohol (primary objective), and the safety of tiopronin in combination with alcohol was tested in healthy volunteers.In this randomised, double-blind, cross-over study, 13 healthy subjects received 500 mg tiopronin or an identical looking placebo 1 h before the intake of 0.8 g of alcohol per kg of bodyweight. Blood alcohol concentrations were measured over the course of 12 h after consumption. The experiment was repeated 7 days later with the previous placebo group receiving the active drug and vice-versa. Changes in blood alcohol AUC and elimination rate k were analysed using a 2-tailed t-test. Further acetaldehyde concentrations were measured. Additionally, the concentration ability of the subjects was tested and any adverse effects were recorded.There was no significant change in blood alcohol or acetaldehyde concentration. Significant differences in concentration tests refer presumably to learning effects. No serious adverse event occurred. All adverse events were reversible and there was no significant difference in occurrence between drug and placebo group.It was demonstrated that tiopronin does not affect the metabolism of alcohol. Intake of tiopronin in combination with alcohol has no safety implications on healthy subjects.

Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates.

Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0–4.92) mg/L, 0.39 (range = 0–72.77) mg/L and in control group infants were 0.15 (range = 0.03–5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0–8.89) mg/L, 0.21 (range = 0–2.43) mg/L and in control group infants were 0.01 (range = 0–0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose.Conclusion: Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates. What is Known: • Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. • However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: • In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. • Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite.

Novel role for carbohydrate responsive element binding protein in the control of ethanol metabolism and susceptibility to binge drinking.

Carbohydrate responsive element binding protein (ChREBP) is central for de novo fatty acid synthesis under physiological conditions and in the context of nonalcoholic fatty liver disease. We explored its contribution to alcohol-induced steatosis in a mouse model of binge drinking as acute ethanol (EtOH) intoxication has become an alarming health problem. Within 6 hours, ChREBP acetylation and its recruitment onto target gene promoters were increased in liver of EtOH-fed mice. Acetylation of ChREBP was dependent on alcohol metabolism because inhibition of alcohol dehydrogenase (ADH) activity blunted ChREBP EtOH-induced acetylation in mouse hepatocytes. Transfection of an acetylation-defective mutant of ChREBP (ChREBP(K672A) ) in HepG2 cells impaired the stimulatory effect of EtOH on ChREBP activity. Importantly, ChREBP silencing in the liver of EtOH-fed mice prevented alcohol-induced triglyceride accumulation through an inhibition of the lipogenic pathway but also led, unexpectedly, to hypothermia, increased blood acetaldehyde concentrations, and enhanced lethality. This phenotype was associated with impaired hepatic EtOH metabolism as a consequence of reduced ADH activity. While the expression and activity of the NAD(+) dependent deacetylase sirtuin 1, a ChREBP-negative target, were down-regulated in the liver of alcohol-fed mice, they were restored to control levels upon ChREBP silencing. In turn, ADH acetylation was reduced, suggesting that ChREBP regulates EtOH metabolism and ADH activity through its direct control of sirtuin 1 expression. Indeed, when sirtuin 1 activity was rescued by resveratrol pretreatment in EtOH-treated hepatocytes, a significant decrease in ADH protein content and/or acetylation was observed. our study describes a novel role for ChREBP in EtOH metabolism and unravels its protective effect against severe intoxication in response to binge drinking.

고농도 산소수로 재배한 콩나물 추출 음료의 알코올 분해 효능

This study was conducted to investigate the detoxification effect of extract from soy-sprout grown using high concentrated oxygen water extract (SE) against alcohol-induced hangover in male Sprague-Dawley (SD) rats. The rats were orally administered with different concentrations of SE beverage [26, 260 and 2,000 ㎎/㎏ body weight (b.w.)] and, after 30 min, with alcohol at a dose of 3 g/㎏ b.w. After 1 and 3 h of alcohol administration, blood was collected from the retroorbital plexus, while after 5 h, blood was collected from the heart. In the 2,000 ㎎/㎏ b.w. SE group, the concentration of blood alcohol was significantly reduced after 1-5 h of alcohol loading as compared with that in the other groups. In addition, the blood acetaldehyde concentration was reduced by SE (2,000 ㎎/㎏ b.w.). These results suggest that SE beverage can alleviate alcohol hangover symptoms by stimulating the activities related to hepatic alcohol-metabolizing enzymes.

Ethanol Induced Urine Acidification is Related with Early Acetaldehyde Concentration

Background Ethanol is worldwide favored beverage among the young adults, but heavy drinking cause many social problems and medical problems such as liver cirrhosis, central nervous system problem. These toxic effects are mainly caused by acetaldehyde, the metabolyte of ethanol. Usual dose of ethanol consumption can cause dehydration and mild metabolic acidosis, there is few experimental human data that explain about the association of blood ethanol and acetaldehyde level and aciduria. We investigated urine electrolyte and pH changes after moderate amount of ethanol ingestion in healthy young men for urine acidification change by ethanol and acetaldehyde level. Materials and Methods 30 Healthy young male volunteers were enrolled with informed consent. They ingested 1.3 g/kg of ethanol in fasting state, and blood and urine samples were taken at before ingestion, 1, 3, 5, 7 hours after ethanol ingestion. Snack was supplied after 4 hours of alcohol intake, and 500 mL of free water was allowed. Urine pH was measured by pH meter and blood and urine electrolytes were measured by indirect method. Blood ethanol was measured by enzymatic method and acetaldehyde was measured by spectrophotometer assay. Results 30 Volunteers were all males, age was 27.40±2.7 years old, body weight was 72.83±7.9 kg. Their usual limit of alcohol intake by history taking were 78.35±56.7 gram, and average amount of ingested ethanol was 98.63±10.7 gram. Blood ethanol concentrations were 0.131, 0.097, 0.098, 0.027% in 1 hr, 3 hrs, 5 hrs, 7 hrs after drinking respectively, and blood acetaldehyde concentrations were 1.480, 1.734, 1.221, 1.462% in 1 hr, 3 hrs, 5 hrs, 7 hrs after drinking respectively. Urine pH were 6.056 in before ethanol ingestion, and 5.724, 5.598 each of 3 hours and 7 hours after ethanol ingestion, respectively. Post-alcohol ingestion urine pH was significantly decreased (p=0.002). Urine sodium and chloride excretions were not changed after ethanol, but urinary potassium excretion was significantly decreased (61.09±25.3 to 40.16±11.9, p Conclusion In conclusion, urine acidification after ethanol ingestion is related with serum acetaldehyde concentration. Early elevation of acetaldhyde could induce urine acidification, but the urine pH was elevated after a few hours, that might make prolonged acidemia.

Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results suggest that higher blood EtOH and acetaldehyde concentrations in ADH1B*2/*2 may constitute the mechanism of protection against alcoholism by ADH1B*2/*2.

Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation.

This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanol-induced hepatic injury. Rats underwent intragastric administration of ethanol (5.0–9.0 g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-κB were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88.

The ameliorating effect of Rosa roxburghii against ethanol-induced psychomotor alterations in rats

Background: Ethanol (EtOH) is one of the oldest recreational substances known to man, primarily taken because it induces a sense of well-being (euphoric effects) and relaxation (anxiolytic effects). EtOH use entails various negative consequences. Of particular interest are EtOH-induced psychomotor alterations, because of its immediate manifestation and adverse consequences. Rosa roxburghii (RR), a wild plant of Southwest China, has gained attention on account of its numerous beneficial effects on the immune, nervous, and cardiovascular systems. Objective: In the present study we assessed the effects of Rosa roxburghii (RR) on EtOH-induced psychomotor alterations in rats. Methods: Sprague Dawley rats were orally administered distilled water (control group) or ethanol (4 g/kg BW) (EtOH-group) to induce psychomotor alterations. RR extract (25, 50, and 100 mg/kg, p.o.) was administered 30 min before EtOH treatment (RR-group). EtOH-induced psychomotor alterations were evaluated in the open-field, accelerating rotarod, hanging wire, and cold swimming tests. Behavioral evaluation and hematological analysis (EtOH and acetaldehyde concentration) were done at 1, 2, 4 and 8 hours after EtOH administration. Results: The EtOH group showed psychomotor alterations as compared with the control group. These EtOH-induced psychomotor alterations were directly related to the rise in blood ethanol and acetaldehyde concentrations. Pre-treatment of RR significantly improved EtOH-induced psychomotor alterations on open-field, accelerating rotarod, hanging wire, and cold swimming tests. These improvements in psychomotor performance coincided with the decreased blood ethanol and acetaldehyde levels observed in the RR-treated group. Conclusion: These results suggest that RR has ameliorating effects against EtOH-induced psychomotor alterations.

Assessment of transpulmonary absorption of ethanol from alcohol-based hand rub

Alcohol-based hand rubs (ABHRs) have been associated with a reduction of nosocomial infections. Despite the worldwide introduction of these products in health care settings, the aim of this study was to assess the transpulmonary absorption of ethanol contains in ABHRs used by health care workers (HCWs) in real conditions of work shift. Twenty-six HCWs of Nancy University Hospital were included. Research consisted in monitoring participants during 4 hours of work shift to assess their exposure to ethanol. The measurement of ethanol vapors in exhaled breath was performed using a class B ethylometer (Alco-Sensor FST). Ethanol concentration in inhaled breath was measured using Gilian pump LFS-113. Concentration of ethanol, acetaldehyde, and acetate in blood and urine samples were determined using gas chromatography with flame ionization detector. Participants were 12% male and 88% female. The mean age was 40 ± 8 years. None of the employees included in the study presented any traces of ethanol or its metabolites in the blood or urine. Ethanol (0.08 ± 0.07 mg/L) was detected in the breath of 10 HCWs at 1 to 2 minutes postexposure. The mean concentration of ethanol in the inhaled air was 46.2 mg/m. Absorption of ethanol vapor from ABHRs among HCWs during their care activities was not detected. Quantification of ethanol fumes inhaled during 4 hours of work shift was below the regulatory limitations of exposure to ethanol.

P.6.a.010 Cognitive disorders among alcoholics: relevance of the Montreal Cognitive Assessment

Acetaldehyde, the first product of ethanol metabolization, is a biologically active compound, but the behavioral properties of acetaldehyde in humans are largely undefined. We investigated the acute effects of both alcohol and acetaldehyde on psychomotor functions related to automobile driving skills.Twenty-four men were selected through genotyping; one-half had the ALDH2*1/*1 (active form) genotype and one-half had the ALDH2*1/*2 (inactive form) genotype. In a double-blind placebo-controlled crossover design, each subject was administered one of the following doses of alcohol: .25 g/kg, .5 g/kg, or .75 g/kg or a placebo in four trials that took place at 1-week intervals. Blood ethanol concentration (BEC) and blood acetaldehyde concentration (BAAC) were measured nine times, and psychomotor function tests (critical flicker fusion threshold, choice reaction time, compensatory tracking task, and digit symbol substitution test) were assessed seven times in total over 4 hours after study drug ingestion.After the consumption of alcohol, BEC was comparable in the two subject groups, whereas BAAC was significantly higher in subjects with ALDH2 *1/*2 than in those with ALDH2 *1/*1. The psychomotor performance of subjects with ALDH2*1/*2 was significantly poorer than that of subjects with ALDH2*1/*1. Significant correlations between psychomotor performance and both BEC and BAAC were observed. However, in the linear regression analysis, BAAC significantly predicted poorer psychomotor performance, whereas BEC was not associated with any measure of psychomotor function.Acetaldehyde might be more important than alcohol in determining the effects on human psychomotor function and skills.

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.

The acute effects of ethanol and acetaldehyde on physiological responses after ethanol ingestion in young healthy men with different ALDH2 genotypes

Background. This study investigated the acute effects of ethanol and acetaldehyde on physiological responses in healthy men according to ALDH2 genotype by measuring them directly in human blood. Methods. Twenty-four men, 12 with the ALDH2*1/*1 genotype and 12 with the ALDH2*1/*2 genotype, were selected. In a double-blind placebo-controlled crossover design, each subject was administered one of three doses of ethanol (0.25, 0.5 or 0.75 g/kg) or a placebo on four separate occasions. The blood ethanol concentration (BEC), blood acetaldehyde concentration (BAAC) and physiological responses including facial redness, pulse rate and systolic and diastolic blood pressures were assessed. Results. Significant differences were observed in the physiological responses between the ALDH2*1/*2 and ALDH2*1/*1 groups. Significant gene effects were observed for pulse rate and facial flushing (F-values = 62.344; p values < 0.001 and F-values = 7.062; p values = 0.010, respectively, by repeated-measures analysis of variance), which were significantly greater in subjects with the ALDH2*1/*2 genotype. In a linear regression analysis, BAAC significantly predicted increased facial redness at 30 minutes (adjusted R: 0.209; p values < 0.001) and pulse rate at 30, 60, 90 and 120 minutes (adjusted R: 0.454, 0.490, 0.428 and 0.193, respectively; all p values < 0.001), whereas BEC was not associated with any physiological response measure at any time. Conclusions. Facial redness and pulse rate after ethanol ingestion were significantly higher in the ALDH2*1/*2 genotype, and were significantly associated with blood acetaldehyde concentrations. The acute effects of ethanol on the physiological responses were mediated mainly by acetaldehyde, the active metabolite of ethanol, rather than by ethanol itself.

Influence of Drinking Conditions on Alcohol Metabolism in Healthy Men with &amp;lt;i&amp;gt;ALDH&amp;lt;/i&amp;gt;2*1/*1 Genotype: Comparison between Different Alcoholic Drinks with or without Meal

The influence of drinking conditions on alcohol metabolism and drunkenness was investigated in healthy men with ALDH2*1/*1 genotype aged from 40 to 60 who were occasional or habitual drinkers. The investigation was performed by open intersection competitive drinking tests at an ethanol dose of 0.32 g/kg under 4 different drinking conditions: beer without a meal [B(–)], shochu (a distilled spirit) without a meal [S(–)], beer with a meal [B(+)] and shochu with a meal [S(+)]. The blood alcohol concentration (BAC) and BAC-AUC (area under the curve) were lower in the B(–) than in the S(–). The blood acetaldehyde concentration (BAcH) and the serum acetate concentration (SAce) were also lower in the B(–) than in the S(–). The meal markedly decreased BAC, BAC-AUC and BAcH-AUC for both alcoholic beverages. Subjective drunkenness was stronger in order of B(+) + in liver cells, was higher in the S(–) than in the B(–), and was decreased by the meal for both alcoholic beverages. These results suggested that glucide increase the rate of alcohol metabolism by supplying pyruvic acid to decrease the ratio of NADH/NAD+, which lowers BAC and relieves drunkenness. Thus, the intake of glucide calories while drinking is important to reduce the pharmacological and toxicological actions of alcohol.

Individual Differences in Blood Alcohol Concentrations after Moderate Drinking Are Mainly Regulated by Gastric Emptying Rate Together with Ethanol Distribution Volume

Blood alcohol concentration (BAC) differs greatly among individuals, even when people of the same sex and age drink alcohol under the same drinking conditions. In this study, we investigated the main factors involved in the internal reg-ulation of individual differences in BAC, focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetal-dehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions. Twenty healthy Japanese males aged between 40 and 59 years old and having the aldehyde dehydrogenase 2 (ALDH2) genotype of ALDH 2*1/*2 were recruited for this study. The subjects were given 0.32 g ethanol/kg body weight in the form of commercially available beer (5%, v/v). The results showed that BAC-max differed greatly among individuals with a more than two-fold variation. When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes. Although BAcH, monthly alcohol consumption, elimination rate of blood ethanol (β value) and ethanol disappearance rate from the body (EDR) can affect BAC, all of them had no correlations with BAC-max. However, Vd (liter/kg), ΔPlasma glucose concentration (ΔPGC = PGC30 min ? PGC0 min) and the serum concentration of gastric inhibitory polypeptide (GIP) did correlate with BAC-max. Model 2 in multiple linear regression analysis showed the optimal model for Vd and GIP with positive correlations with BAC-max. As GIP and ΔPGC are both reflected by gastric emptying rate (GER), we concluded that the individual differences in BAC after moderate drinking are mainly regulated by GER together with Vd. These findings demonstrate that together with body water content, the gastrointestinal tract plays an important role in the regulation of individual differences in BAC, involving first pass metabolism of ethanol.

Patterns of the most abundant volatiles detected in post-mortem blood

The most abundant volatiles detected during the forensic ethanol analysis are ethanol, acetaldehyde, 1-propanol, 2-propanol, and acetone. These volatiles could either be initiated in the human body after the consumption of alcoholic beverages; or have been produced ante mortem during metabolic processes or post-mortem by microbes. Aims of this study were the determination of the volatiles' concentrations in autopsy blood samples received from 483 routinely autopsied corpses and classification of their patterns according to the manner of death, and the presence of putrefaction at autopsy. The volatiles concentrations were determined by a validated gas chromatographic method. The experimental values obtained from these determinations were submitted to statistical evaluation by principal component analysis (PCA). Blood acetaldehyde, acetone, 1- and 2-propanol concentrations were higher in cases of violent and undetermined deaths compared to the ones determined in cases of natural deaths. Blood volatiles concentrations were dispersed in higher values in cases with putrefaction compared to cases without putrefaction at autopsy. Blood volatiles had low values in the majority of cases with low BAC. All volatiles had higher maximum concentrations and broader concentration ranges when BAC ranged from 10-100 mg/ dL. Cases of undetermined manner of death along with some cases of violent deaths achieved clustering (PCA) from cases of violent or natural manner of death indicating similarities among the grouped samples on the basis of measured blood 1-propanol and ethanol concentrations. The latter novel finding needs further investigation using a larger dataset pool and possibly other classification method with a different regression model.

Tryptophan in Alcoholism Treatment II: Inhibition of the Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Activity, Elevation of Blood Acetaldehyde Concentration and Induction of Aversion to Alcohol by Combined Administration of Tryptophan and Benserazide

Aims: The aims were to provide proofs of mechanism and principle by establishing the ability of the amino acid L-tryptophan (Trp) combined with the kynureninase inhibitor benserazide (BSZ) to inhibit the liver mitochondrial low Km aldehyde dehydrogenase (ALDH) activity after administration and in vivo and to induce aversion to alcohol. Methods: Trp, BSZ or both were administered to male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring acetaldehyde accumulation in blood after ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice. Results: Combined administration of Trp + BSZ, but neither compound alone, produced a strong inhibition of ALDH activity and an increase in blood acetaldehyde concentration after ethanol, and induced aversion to alcohol in rats and decreased preference in mice. Another kynureninase inhibitor, carbidopa, induced aversion to alcohol by itself, which was reversed by Trp co-administration. Conclusions: The present results establish a prior art for the use of a combination of Trp plus BSZ in the treatment of alcoholism by aversion, which merits rapid clinical development.

Tryptophan in alcoholism treatment I: kynurenine metabolites inhibit the rat liver mitochondrial low Km aldehyde dehydrogenase activity, elevate blood acetaldehyde concentration and induce aversion to alcohol.

Aims: The aims were to provide proofs of mechanism and principle by establishing the ability of kynurenine metabolites to inhibit the liver mitochondrial low Km aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to induce aversion to alcohol. Methods: Kynurenic acid (KA), 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice. Results: ALDH activity was significantly inhibited by all three metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation after ethanol administration was strongly elevated by KA and 3-HK and to a lesser extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and decreased alcohol preference in mice. Conclusions: The above kynurenine metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity. An intellectual property covering the use of 3-HK and 3-HAA and derivatives thereof in the treatment of alcoholism by aversion awaits further development.

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.