Effect Modification of Acetaldehyde Dehydrogenase 2 rs671 Polymorphism on the Association between Alcohol Intake and Blood Pressure: the Dong-gu Study

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes.METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed.RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91–1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15–1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women.CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.

Análise histológica do estômago da prole de ratas Wistar submetidas ao consumo crônico de álcool durante a prenhez / Histological analysis of stomach of offspring of Wistar rats submitted to chronic alcohol consumption during pregnancy

O consumo de bebidas alcoólicas na gravidez consiste em um importante problema de saúde pública, visto que, pode causar prejuízos na organogênese de diversos órgãos, incluindo o estômago, entretanto, poucos estudos avaliam o efeito da exposição pré-natal ao álcool nesse órgão. O objetivo deste estudo foi analisar histologicamente o estômago da prole de ratas submetidas ao consumo crônico de álcool durante a prenhez. Utilizou-se 10 ratas prenhes divididas nos grupos: Controle - ratas que receberam água destilada durante todo período gestacional e Álcool ­ ratas que receberam álcool etílico absoluto (3g/kg/dia) durante todo período gestacional. Logo após o nascimento, 12 neonatos (6 machos e 6 fêmeas) de cada grupo foram anestesiados e os estômagos coletados. Posteriormente, os órgãos foram fixados e processados seguindo a técnica histológica de rotina. Foram feitas análises histomorfométricas das camadas mucosa, muscular e da parede total do estômago. Observou-se que as proles macho e fêmea expostas ao etanol apresentaram diminuição da área de epitélio, contudo, os machos também mostraram redução significativa do número de células epiteliais. Demonstrou-se ainda redução na espessura das camadas mucosa, muscular e da parede total do estômago da prole fêmea do grupo Álcool. No entanto, a camada muscular apresentou aumento significativo em sua espessura no grupo de neonatos machos expostos ao etanol. Assim, concluímos que a exposição pré-natal ao álcool provoca efeitos nocivos sobre o estômago dos neonatos, contudo, estudos futuros são necessários para melhor elucidar os mecanismos envolvidos na patogênese e possíveis consequências para os animais na fase adulta.

Consumption of alcoholic beverages during pregnancy is a significant public health issue since it can damage the organogenesis of several organs, including the stomach; however, few studies evaluate the effect of prenatal exposure to alcohol in this organ. The objective of this study was to analyze the histology of the stomach of offspring of rats submitted to chronic alcohol consumption during pregnancy. Ten pregnant rats were divided into two groups: Control - rats receiving distilled water throughout the gestation period, and Alcohol - rats receiving absolute ethyl alcohol (3g/kg/day) throughout the gestation period. After birth, 12 newborn rats (6 males and 6 females) from each group were anesthetized and their stomachs were collected. Subsequently, the organs were fixed and processed following the routine histological technique. The mucosa, muscle and total stomach were submitted to histomorphometric analyses. It was observed that the male and female offspring exposed to ethanol had a decrease in the epithelium area. However, males also showed a significant reduction in the number of epithelial cells. There was also a reduction in the layer's thickness mucosa, muscle and total stomach wall of the female offspring from the alcohol group. Additionally, the muscular layer presented a significant increase in its thickness in the group of male neonates exposed to ethanol. It can be concluded that prenatal exposure to alcohol causes harmful effects on neonates' stomachs; however, future studies are necessary to better elucidate the mechanisms involved in the pathogenesis and possible consequences for the animals in adulthood.

Relationship between acetaldehyde concentration in mouth air and characteristics of microbiota of tongue dorsum in Japanese healthy adults: a cross-sectional study

Abstract Acetaldehyde, associated with consumption of alcoholic beverages, is known to be a carcinogen and to be related to the tongue dorsum. Objective The aim of this study was to investigate the relationship between acetaldehyde concentration in mouth air and bacterial characteristics on the tongue dorsum. Methodology Thirty-nine healthy volunteers participated in the study. Acetaldehyde concentrations in mouth air were evaluated by a high-sensitivity semiconductor gas sensor. A 16S rRNA gene sequencing technique was used to compare microbiomes between two groups, focusing on the six samples with the highest acetaldehyde concentrations (HG) and the six samples with lowest acetaldehyde concentrations (LG). Results Acetaldehyde concentration increased in correlation with the increase in bacterial count (p=0.048). The number of species observed in the oral microbiome of the HG was higher than that in the oral microbiome of the LG (p=0.011). The relative abundances of Gemella sanguinis, Veillonella parvula and Neisseria flavescens in the oral microbiome of the HG were higher than those in the oral microbiome of the LG (p<0.05). Conclusion Acetaldehyde concentration in mouth air was associated with bacterial count, diversity of microbiome, and relative abundance of G. sanguinis, V. parvula, and N. flavescens.

Epileptic Seizure Due to Disulfiram Treatment / 가정의학회지

Disulfiram has been used for the treatment of alcohol dependence for nearly 65 years and is approved by the Food and Drug Administration. It causes negative reinforcement by accumulating toxic acetaldehyde due to irreversible inhibition of aldehyde dehydrogenase. Disulfiram has very few side effects when taken without alcohol. Epileptic seizure induction is a rare side effect in therapeutic doses, and its mechanism is unknown. We present a patient with a single epileptic seizure which was thought to be due to disulfiram used in the treatment of alcohol dependence. We did not find it ethical to administer disulfiram again because the patient discontinued alcohol use and was afraid of epileptic seizures.

Relationship between Blood Acetaldehyde Concentration and Psychomotor Function of Individuals with Different ALDH2 Genotypes after Alcohol Consumption / 法医学杂志

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 SNaPshotTM 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.

Pilot Study of a Brief WeChat Intervention in China to Increase Students' Willingness to Assist a Flushing Student to Reduce Alcohol Use / 예방의학회지

OBJECTIVES: This pilot study tested the effectiveness of a brief alcohol-related intervention delivered by the social media app WeChat to teach about ethanol-induced facial flushing and increase the willingness of students who see another student flushing to suggest that he or she should reduce or stop drinking. In the context of Chinese drinking culture, it is sometimes socially difficult to refuse a drink, even when experiencing physical discomfort, such as flushing. METHODS: Classrooms of students in a medical university in China were randomly assigned to the intervention or control group. Students in the intervention group were invited to view 3 alcohol education lessons on WeChat during a 2-week period. A pretest and posttest before and after the 2-week period assessed changes in students’ willingness to intervene if they saw someone flush while drinking. Data were collected about students’ alcohol use and their ratings of the lessons. RESULTS: Mixed-design analysis of variance yielded a significant time-by-treatment interaction effect on the variable of willingness to suggest that a flushing person stop or slow down their drinking, and the change was significant between the intervention and control groups. One-way analysis of covariance yielded a significant treatment effect at the posttest, after controlling for the pretest score. Students rated the lessons above the midpoint of the scale for being informative, interesting, and useful. CONCLUSIONS: The pilot study showed that a brief alcohol-related intervention delivered by WeChat could produce a measurable positive change in the willingness of university students to suggest that a student who flushes should stop drinking. This pilot study also suggested improvements for future lessons and evaluation design.

Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats / 한국실험동물학회지

Hangover is characterized by a number of unpleasant physical and mental symptoms that occur after heavy alcohol drinking. In addition, consistently excessive alcohol intake is considered as a major reason causes liver disease. The present study investigated the in vivo effects of DA-5513 (Morning care® Kang Hwang) on biological parameters relevant to hangover relief and alcoholic fatty liver. Blood alcohol and acetaldehyde concentrations were determined in rats administered a single dose of alcohol and treated with DA-5513 or commercially available hangover relief beverages (Yeomyung® and Ukon®). The effects of DA-5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and alanine aminotransferase activities) and serum/liver lipid levels were assessed. Blood alcohol and acetaldehyde concentrations were lower in the groups treated with DA-5513 or Yeomyung®, as compared with control rats. However, Ukon® did not produce any significant effects on these parameters. Treatment with DA-5513 significantly reduced serum aspartate and alanine aminotransferase activities and markedly reduced serum cholesterol and triglyceride levels, as compared with control rats. Histological observations using Oil Red O staining found that DA-5513 delayed the development of alcoholic fatty liver by reversing hepatic fat accumulation. These findings suggest that DA-5513 could have a beneficial effect on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty liver.

Pathophysiology and Management of Alcoholic Liver Disease: Update 2016

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.

Associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length in Korean adults

BACKGROUND/OBJECTIVES: Telomere length is a useful biomarker for determining general aging status. Some studies have reported an association between alcohol consumption and telomere length in a general population; however, it is unclear whether the alcohol flush reaction, which is an alcohol-related trait predominantly due to acetaldehyde dehydrogenase deficiency, is associated with telomere length. This cross-sectional study aimed to evaluate the associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length (LTL). SUBJECTS/METHODS: The study included 1,803 Korean adults. Participants provided blood specimens for LTL measurement assay and reported their alcohol drinking status and the presence of an alcohol flush reaction via a questionnaire-based interview. Relative LTL was determined by using a quantitative polymerase chain reaction. Statistical analysis used multiple linear regression models stratified by sex and age groups, and potential confounding factors were considered. RESULTS: Age-specific analyses showed that heavy alcohol consumption (> 30 g/day) was strongly associated with a reduced LTL in participants aged ≥ 65 years (P 15 g/day of alcohol (P < 0.01). No significant alcohol consumption or alcohol flush reaction associations with LTL were observed in the sex-specific analyses. CONCLUSIONS: The results suggest that older alcohol drinkers, particularly those with the alcohol flush reaction, may have an accelerated aging process.

Study of the removal difference in indoor particulate matter and volatile organic compounds through the application of plants

This study was conducted to evaluate the ability of plants to purify indoor air by observing the effective reduction rate among pollutant types of particulate matter (PM) and volatile organic compounds (VOCs). PM and four types of VOCs were measured in a new building that is less than three years old and under three different conditions: before applying the plant, after applying the plant, and a room without a plant. The removal rate of each pollutant type due to the plant was also compared and analyzed. In the case of indoor PM, the removal effect was negligible because of outdoor influence. However, 9% of benzene, 75% of ethylbenzene, 72% of xylene, 75% of styrene, 50% of formaldehyde, 36% of acetaldehyde, 35% of acrolein with acetone, and 85% of toluene were reduced. The purification of indoor air by natural ventilation is meaningless because the ambient PM concentration has recently been high. However, contamination by gaseous materials such as VOCs can effectively be removed through the application of plants.

Hangover relieving effect of Sanghwang mushroom mycelium cultured in germinated buckwheat

The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of 16 µL/mL. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol (40.02 ± 33.38 µg/mL, 66.01 ± 22.04 µg/mL, respectively) and aldehyde (5.72 ± 0.47 µg/mL, 6.72 ± 1.70 µg/mL, respectively) concentrations in blood compared to those in the alcohol-water group (199.75 ± 33.83 µg/mL, 50.43 ± 13.88 µg/mL, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

Study of the removal difference in indoor particulate matter and volatile organic compounds through the application of plants

This study was conducted to evaluate the ability of plants to purify indoor air by observing the effective reduction rate among pollutant types of particulate matter (PM) and volatile organic compounds (VOCs). PM and four types of VOCs were measured in a new building that is less than three years old and under three different conditions: before applying the plant, after applying the plant, and a room without a plant. The removal rate of each pollutant type due to the plant was also compared and analyzed. In the case of indoor PM, the removal effect was negligible because of outdoor influence. However, 9% of benzene, 75% of ethylbenzene, 72% of xylene, 75% of styrene, 50% of formaldehyde, 36% of acetaldehyde, 35% of acrolein with acetone, and 85% of toluene were reduced. The purification of indoor air by natural ventilation is meaningless because the ambient PM concentration has recently been high. However, contamination by gaseous materials such as VOCs can effectively be removed through the application of plants.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism. Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks. Mendelian randomization (MR) studies have demonstrated that alcohol consumption predicted by ALDH2 genotype is causally related to cardiovascular risks. Moreover, recent MR studies suggest that the ALDH2 variant has mechanistic effects on some disease outcomes or mortality through increased blood levels of acetaldehyde, showing differences therein between heterozygotes (ALDH2*2*2) and homozygotes (ALDH2*1*2) in those who consume alcohol. Accordingly, consideration of ALDH2 genotype in alcohol prevention programs is warranted. In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required.

Prevalencia de intento de suicidio adolescente y factores de riesgo asociados en una comuna rural de la provincia de Concepción / Suicide attempts among Chilean adolescents

Background: Suicide mortality rates are increasing among teenagers. Aim: To study the prevalence and predictive factors of suicide attempts among Chilean adolescents. Material and Methods: A random sample of 195 teenagers aged 16 ± 1 years (53% males) answered an anonymous survey about their demographic features, substance abuse, the Osaka suicidal ideation questionnaire, Smilksten familial Apgar. Beck hopelessness scale, Beck depression scale and Coppersmith self-esteem inventory. Results: Twenty five percent of respondents had attempted suicide at least in one occasion during their lives. These attempts were significantly associated with female gender, absent parents, family dysfunction, drug abuse, smoking, low self-esteem, hopelessness, depression and recent suicidal ideation. A logistic regression analysis accepted female gender, smoking and recent suicidal ideation as significant independent predictors of suicide attempt. Conclusions: Suicide attempted is common among teenagers and its predictors are female sex, smoking and previous suicidal ideation.

Relationship between acetaldehyde concentration in mouth air and tongue coating volume

Objective Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Material and Methods Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Results Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Conclusion Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume. .

Effect of ethanol and its metabolites on acetylcholine-sensitive K(+) channel Kir3.1 protein expression of neonatal rat primary atrial cardiomyocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify the effect of ethanol and its metabolite acetaldehyde on acetylcholine-sensitive K(+) channel Kir3.1 protein expression, and explore the potential role of this channel and acetaldehyde in arrhythmia caused by acute alcoholic intoxication.</p><p><b>METHODS</b>Primary atrial cardiomyocytes were isolated from 150 newborn SD rats by typsin and type II collagenase, cultured and troponin I was determined by immunofluorescence. Cell survival in 200-800 mmol/L ethanol or 50-500 µmol/L acetaldehyde treated cells for 24 hours was measured by CCK-8 assay to determine the concentration of ethanol and acetaldehyde for inducing apoptosis in cardiomyocytes. The highest non-apoptotic concentration (200 mmol/L) of ethanol and acetaldehyde (100 µmol/L) was used in the main study. Kir3.1 protein expression was detected by Western blot.</p><p><b>RESULTS</b>(1) Cellular immunofluorescence results showed that cultured cells are cardiomyocytes, and more than 90% of these cells are troponin I positive. (2) CCK-8 assay demonstrated that the survival rate of cardiomyocytes in the groups treated by ethanol over 400 mmol/L for 24 hours or acetaldehyde over 400 µmol/L was significantly lower than that of the control group (P < 0.05), while the survival rate was similar in cardiomyocytes treated by ethanol less than 200 mmol/L or acetaldehyde less than 350 µmol/L for 24 hours and the control group (P > 0.05). (3) Western-bolt assay revealed that ethanol and acetaldehyde treatment for 24 hours upregulated Kir3.1 protein expression in primary atrial cardiomyocytes of newborn SD rats by (44.52 ± 23.07)% and (45.04 ± 22.01)% respectively compared with the control group (all P < 0.01).</p><p><b>CONCLUSIONS</b>Acute ethanol and acetaldehyde treatment could significantly upregulate the protein expression of acetylcholine-sensitive K(+) channel Kir3.1, this might serve as a potential mechanism for arrhythmia caused by acute alcoholic intoxication.</p>

Effect of the Mixture of Pueraria lobata and Sorbus commixta Extract on the Alcohol-induced Hangover in Rats

Pueraiae Radix (PR), Pueratia Folium (PF) and Sorbus commixta (SC) mixture, namely GS-SP (PR (1)/PF (2)/SC (0.5): v/v/v) was developed as hangover-relieving elixir and its effects on alcoholic metabolism have been investigated. The enzymatic activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) of GS-SP was shown higher than those of single treatment with PR, PL, SC, and the positive control group (YM-808). The survival rate of mouse liver cell line NCTC clone 1469 in the presence of acetaldehyde was 30.6, 22.2, and 8.7% at the GS-SP dosage level of 50, 100, and 200 microg/mL respectively. Different concentrations of 50, 100 and 200 mg/kg of GS-SP showed efficient activity for ADH and ALDH than YM-808 in rat fed with 25% ethanol. The levels of blood alcohol and acetaldehyde after oral administration of 200 mg/kg of GS-SP showed efficient activity of 11.7% and 37% than those of YM-808. These results have been supported to the potential for GS-SP to serve as an excellent potential in providing hangover relief and liver protection.

Acumulación de acetaldehído y estrés oxidativo en testículo luego de la intoxicación alcohólica en ratas / High levels of acetaldehyde and oxidative stress in rat testes after alcohol drinking / Acúmulo de acetaldeído e estresse oxidativo em testículo de ratos após intoxicação alcoólica

En el hombre el consumo excesivo de alcohol está asociado con una disminución en la producción de testosterona y la atrofia testicular. Pudieron observarse consecuencias similares en estudios realizados in vitro en testículos aislados y la producción de testosterona, donde el acetaldehído mostró ser más potente que el alcohol para la supresión de la liberación de la hormona. Estudios previos de este laboratorio reportaron que la fracción microsomal del testículo de rata era capaz de metabolizar el etanol a metabolitos reactivos como el acetaldehído y los radicales libres 1-hidroxietilo. En este trabajo se presenta evidencia de que luego de una dosis única de etanol, el acetaldehído se acumula en el testículo durante las primeras seis horas posteriores al tratamiento para alcanzar concentraciones superiores a las plasmáticas aunque más bajas que en el hígado. Además se encontró que la actividad aldehído deshidrogenasa presente en el testículo es significativamente menor que en el hígado. El consumo de etanol en los animales produjo una susceptibilidad aumentada a la oxidación de los lípidos testiculares, que fue detectada por niveles aumentados de hidroperóxidos de lípidos. Los resultados sugieren que la oxidación in situ del etanol a acetaldehído y a radicales libres y la detoxificación deficiente podrían ser relevantes para explicar los efectos observados.

Excessive alcohol consumption is associated with impaired testosterone production and testicular atrophy. Similar findings were observed in in vitro studies on testosterone production by isolated testes, being acetaldehyde more potent than alcohol in suppressing testosterone release. In previous laboratory studies, it was reported that rat testicular microsomes were able to bioactivate ethanol to reactive metabolites like acetaldehyde and 1-hydroxyethyl free radical. In this work, evidence is shown that after a single ethanol dose, acetaldehyde accumulates in testicular tissue during the first six hours post-treatment to reach concentrations higher than those in blood but lower than those in the liver. In agreement with those findings, it was reported that aldehyde dehydrogenase activity in cytosolic, mitochondrial and microsomal fractions is significantly smaller than in the corresponding liver counterparts. Ethanol drinking led to increased susceptibility of testicular lipids to oxidation as detected by increased levels of microsomal lipid hydroperoxides. Results suggest that in situ oxidation of ethanol to acetaldehyde and free radicals and their poor detoxification would be relevant to the effects observed.

No homem, o consumo excessivo de álcool está associado a uma diminuição da produção de testosterona e atrofia testicular. Efeitos semelhantes foram observados em estudos realizados in vitro em testículos isolados e na produção de testosterona, em que o acetaldeído se mostrou mais potente do que o álcool para a supressão da liberação do hormônio. Estudos anteriores deste laboratório referiram que a fração microssomal do testículo de camundongo era capaz de metabolizar etanol para metabolitos reativos como o acetaldeído e os radicais livres 1-hidroxietil. Este trabalho apresenta evidência de que após uma dose única de etanol o acetaldeído se acumula no testículo durante as primeiras seis horas após o tratamento para atingir concentrações superiores às plasmáticas embora mais baixas que no fígado. Constatou-se também que a atividade aldeído desidrogenase presente no testículo é significativamente menor do que no fígado. O consumo de etanol nos animais produziu uma susceptibilidade aumentada à oxidação dos lipídeos testiculares, que foi detectada por níveis aumentados de hidroperóxidos de lipídeos. Os resultados sugerem que a oxidação in situ de etanol a acetaldeído e a radicais livres e a desintoxicação deficiente poderiam ser relevantes para explicar os efeitos observados.

Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.

Alcohol consumption and the risk of breast cancer

Epidemiologic studies addressing the association of alcohol consumption with breast cancer consistently suggest a modest association and a dose-response relationship. The epidemiologic evidence does not point to a single mechanism to explain the association, and several mechanisms have been proposed. Alcohol consumption is shown to increase levels of endogenous estrogens, known risk factors for breast cancer. This hypothesis is further supported by data showing that the alcohol-breast cancer association is limited to women with estrogen-receptor positive tumors. Products of alcohol metabolism are known to be toxic and are hypothesized to cause DNA modifications that lead to cancer. Recent research has focused on genes that influence the rate of alcohol metabolism, with genes that raise blood concentrations of acetaldehyde hypothesized to heighten breast cancer risk. Mounting evidence suggests that antioxidant intake(e.g.folate)mayreducealcohol-associatedbreast cancer risk, because it neutralizes reactive oxygen species, a second-stage product of alcohol metabolism. Diets lacking sufficient antioxidant intake, as a result, may further elevate the risk of breast cancer among alcohol consumers. Given that alcohol consumption is increasing worldwide and especially among women in countries of rapid economic growth, a greater understanding of the mechanisms underlying the known alcohol-breast cancer association is warranted.Avoiding overconsumption of alcohol is recommended, especially for women with known risk factors for breast cancer.

Diversos estudios epidemiológicos muestran la asociación del consumo de alcohol con el cáncer de mama de forma consistente, lo que sugiere una modesta asociación, y una relación de dosis-respuesta.La evidencia no apunta a un mecanismo único para explicar la asociación y varios mecanismos han sido propuestos. El consumo de alcohol incrementa los niveles endógenos de estrógeno, un riesgo conocido para cáncer de mama. Esta hipótesis es apoyada por información que muestra que la asociación entre el alcohol y el cáncer de mama está limitada a mujeres con tumores con receptores positivos de estrógeno. Es conocido que los derivados de la metabolización del alcohol son tóxicos, y se ha pensado que causan modificaciones en el DNA que llevan al cáncer. La investigación reciente se ha enfocado en genes que influencian la velocidad con la que se metaboliza el alcohol, y elevan las concentraciones de acetaldehído que se piensa puede aumentar el riesgo de cáncer de mama. La evidencia actual sugiere que la ingesta de antioxidantes (e.g. folato) puede reducirelriesgode cáncer asociadoalalcohol,porque neutraliza las especies reactivas de oxígeno, un producto de la segunda etapa del metabolismo del alcohol. Las dietas con ingesta insuficiente de antioxidantes,como resultado de esto, pueden elevar el riesgo de cáncer entre los consumidores de alcohol.Dado que el consumo de alcohol está incrementando en todo el mundo, especialmente en mujeres de países con rápido crecimiento económico, un mejor entendimiento de los mecanismos subyacentes a la asociación del cáncer de mama y el alcohol es necesario. Evitar el consumo excesivo es recomendado, especialmente para mujeres con factores de riesgo conocidos para cáncer de mama.