No abstract available.
Alcoholics* ; Aldehyde Dehydrogenase* ; Humans ; Liver Diseases, Alcoholic*

Aldehyde dehydrogenase 2 (ALDH2), as one of the most important alcohol metabolizing enzymes, plays a significant role in the detoxification process of acetaldehyde which is a main carcinogenic product of alcoholic metabolism. Alteration in its genotypes (particularly at the site of rs671) is closely associated with a variety of tumors in drinkers. Recent advance in the research of the association of the ALDH2 gene rs671 polymorphisms with cancer susceptibility in drinkers is reviewed.
Alcohol Drinking ; genetics ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; etiology ; genetics ; Polymorphism, Genetic

OBJECTIVE: To explore alcohol pharmacokinetics as well as acetaldehyde level in peripheral blood in human subjects with different ALDH2 genotypes after drinking. METHODS: Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length polymorphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. RESULTS: According to the results of electrophoresis, 5 people carried ALDH2*1/*1 as wild group and 9 people carried ALDH2*1/*2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7 microg/mL and 0-5.1772 microg/mL, respectively. The AUC values of alcohol and acetaldehyde and the t1/2Z value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group (P<0.05). CONCLUSION After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2*1/*2 mutation group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.
Alcohol Drinking ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Ethanol/metabolism* ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic

Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshot^TM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.
Acetaldehyde/metabolism* ; Alcohol Drinking/blood* ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Aldehyde Oxidoreductases ; Ethanol/metabolism* ; Genotype ; Humans ; Polymorphism, Genetic/genetics* ; Psychomotor Performance/physiology*

To evaluate the concentration-time profiles of breath ethanol in degradation phase in proportion to the amount of alcohol, we carried out the controlled drinking study for 24 healthy males. Studies are performed three times in the interval of two weeks. Before the experiment, we analyzed alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) to compare with the degradation rate. All subjects are classified into three groups considering past alcohol-drinking history. Group A subjects (n = 6) consumed 0.25, 0.5 and 0.75 g ethanol kg of body weight, group B subjects (n = 9) 0.5, 0.75 and 1.0 g, and group C subjects (n = 9) 0.75, 1.0 and 1.25 g in fasting state, respectively. Breath alcohol samples were examined from 30 minutes to 5 hour every 30-60 minutes after the alcohol intake. Statistical analysis of breath alcohol concentration (BrAC) values obtained. Concentration-time profiles of alcohol were plotted for each subject and the rate of degradation of breath was determined using linear regression analysis. According to the mean of corrected regression lines, disappearance rate of BrAC is calculated in A group: 0.0101 +/- 0.000232% (v/v), B group: 0.0093 +/- 0.000133% (v/v), C group: 0.0099 +/- 0.000121% (v/v).
Alcohol Dehydrogenase ; Aldehyde Dehydrogenase ; Body Weight ; Drinking ; Ethanol ; Fasting ; Humans ; Linear Models ; Male

OBJECTIVETo study the distribution of aldehyde dehydrogenase-2 (ALDH2) polymorphisms between healthy Zhuang and Han ethnic individuals in Guangxi Autonomous Region and its influence to the behaviors of alcohol consumption.

METHODSPolymerase chain reaction with confronting two-pair primers (PCR-CTPP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to genotype ALDH2, respectively, and alcohol consumption was recorded in a constructed questionnaire.

RESULTSThe frequencies of ALDH2 alleles (ALDH2(1)/ALDH2(2)) among Zhuang and Han ethnics were 0.511, 0.489 and 0.508, 0.492 respectively (chi2 = 0.001, P > 0.05). The ALDH2 genotypes were verified with PCR-RFLP method. The frequencies of ALDH2(1) genotype in alcoholics (> or = 3 times drinking per week) were 35.59% and 15.67% in Zhuang and Han groups respectively (chi2 = 5.800, P = 0.016).

CONCLUSIONThere was no significant different distribution of ALDH2 genotype among healthy Zhuang and Han ethnic people. The genotype of ALDH2 in different ethnicity might influence individual behavior of alcohol consumption.

Adult ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Alleles ; China ; DNA Primers ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length

BACKGROUNDNitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population.

METHODSThis study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes.

RESULTSBoth CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05).

CONCLUSIONALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Aged ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Asian Continental Ancestry Group ; Female ; Hemodynamics ; drug effects ; genetics ; physiology ; Humans ; Male ; Middle Aged ; Nitroglycerin ; pharmacology ; Polymorphism, Genetic ; genetics

OBJECTIVETo observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/ R) injury in diabetic rats.

METHODSDiabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups (n = 8). After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glycosylated hemoglobin (HbA1c) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.

RESULTSIn contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/- dp/dtmax) and left ventricular work (RPP) were decreased, left ventricular end diastolic pressure (LVEDP) and LDH release were increased, and ALDH2 mRNA and protein expressions were decreased; compared with I/R in diabetic rat, ALDH2 agonist ethanol significantly promoted the recovery of LVDP, +/- dp/dtmax, RPP, reduced HbA1c level, LVEDP and LDH released, ALDH2 mRNA and protein expressions were increased.

CONCLUSIONIn diabetic rat, the expression of ALDH2 was decreased when heart was subjected to I/R. Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate whether autophagy mediates the effects of aldehyde dehydrogenase 2 (ALDH2) on the proliferation of neonatal rat cardiac fibroblasts cultured in high glucose. METHODS: Cardiac fibroblasts were isolated from neonatal (within 3 days) SD rats and subcultured. The fibroblasts of the third passage, after identification with immunofluorescence staining for vimentin, were treated with 5.5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), or 30 mmol/L glucose in the presence of Alda-1 (an ALDH2 agonist), daidzin (an ALDH2 2 inhibitor), or both. Western blotting was employed to detect ALDH2, microtubule-associated protein 1 light chain 3B subunit (LC3B) and Beclin-1 in the cells, and a hydroxyproline detection kit was used for determining hydroxyproline content in cell culture medium; CCK- 8 kit was used for assessing the proliferation ability of the cardiac fibroblasts after the treatments. RESULTS: Compared with the control cells, the cells exposed to high glucose exhibited obviously decreased expressions of ALDH2, Beclin-1 and LC3B and increased cell number and hydroxyproline content in the culture medium. Treatment of the high glucose-exposed cells with Alda-1 significantly increased Beclin-1, LC3B, and ALDH2 protein expressions and lowered the cell number and intracellular hydroxyproline content, whereas the application of daidzin resulted in reverse changes in the expressions of ALDH2, Beclin-1 and LC3B, viable cell number and intracellular hydroxyproline content in high glucose-exposed cells. CONCLUSIONS Mitochondrial ALDH2 inhibits the proliferation of neonatal rat cardiac fibroblasts induced by high glucose, and the effect is possibly mediated by the up-regulation of autophagy-related proteins Beclin-1 and LC3B.
Aldehyde Dehydrogenase ; Aldehyde Dehydrogenase, Mitochondrial ; metabolism ; Animals ; Animals, Newborn ; Autophagy ; Beclin-1 ; physiology ; Fibroblasts ; Glucose ; Microtubule-Associated Proteins ; Mitochondrial Proteins ; Rats ; Rats, Sprague-Dawley

The protective effect of EtOAc fraction of Limonium tetragonum extract (EALT) against alcoholinduced hepatotoxicity was assessed following acute ethanol intoxication in Spraque-Dawley rats. EALT (200 mg/kg p.o.) was administrated once before alcohol intake (8 g/kg, p.o.). Blood ethanol concentration, and the activities of alcohol metabolic enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were measured. Also, the formation of malondialdehyde (MDA) and the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase were determined after acute alcohol exposure. Pretreatment of rats received ethanol with EALT significantly decreased blood ethanol concentration and elevated the activities of ADH and ALDH in liver. The increased MDA level was decreased, and the reduced activities of SOD, GSH-px and catalase were markedly preserved by the treatment with EALT. This study suggests that EALT prevent hepatic injury induced by acute alcohol which is likely related to its modulation on the alcohol metabolism and antioxidant enzymes activities.
Alcohol Dehydrogenase ; Aldehyde Dehydrogenase ; Animals ; Catalase ; Ethanol* ; Glutathione Peroxidase ; Liver* ; Malondialdehyde ; Metabolism* ; Plumbaginaceae* ; Rats ; Salt-Tolerant Plants ; Superoxide Dismutase