Increased Acetaldehyde Levels Research Articles

The interplay of the oral microbiome and alcohol consumption in oral squamous cell carcinomas.

Oral cancer (OC) is among the top twenty occurring cancers in the world, with a mortality rate of 50%. A shift to a functionally inflammatory or a 'disease state' oral microbiome composition has been observed amongst patients with premalignant disorders and OC, with evidence suggesting alcohol could be exacerbating the inflammatory influence of the oral microorganisms. Alcohol dehydrogenase (ADH, EC 1.1.1.1) converts alcohol into a known carcinogenic metabolite, acetaldehyde and while ADH levels in oral mucosa are low, several oral commensal species possess ADH and could produce genotoxic levels of acetaldehyde. With a direct association between oral microbiome status, alcohol and poor oral health status combining to induce chronic inflammation with increased acetaldehyde levels - this leads to a tumour promoting environment. This new disease state increases the production of reactive oxygen species (ROS), while impairing anti-oxidant systems thus activating the redox signalling required for the promotion and survival of tumours. This review aims to highlight the evidence linking these processes in the progression of oral cancer.

Acetaldehyde reactions during wine bottle storage

Acetaldehyde is a major wine oxidation product. Here, three Cabernet Sauvignon wines, containing different levels of acetaldehyde from different micro-oxygenation (mOx) regimes, including yeast-mediated treatments, were aged under closures differing in oxygen ingress. Oxygen, phenolics, carbonyls and heterocyclic acetals were measured. Acetaldehyde levels at bottling was a significant factor in the phenolic compound profile after one year, with anthocyanins most affected, then flavonols, flavonoids and hydroxycinnamic acids, but there were negligible effects on benzoic acids. The effect of bottle closures with increased oxygen ingress had a similar trend. Increased acetaldehyde levels and oxygen ingress also yielded higher levels of the heterocyclic acetals from glycerol. These changes reflect aging, and suggest that managing mOx during production could be used to reduce the time needed to achieve some aged wine characteristics.

DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil.

DNA damage caused by the accumulation of bio-products generated in the biotransformation of ethanol to acetaldehyde mediated by the CYP2E1 enzyme has been studied. To evaluate DNA damage in peripheral blood lymphocytes and the possible association with polymorphisms in the promoter region of the CYP2E1 gene, we performed a case-control study including 75 alcoholics and 59 individuals who consume alcohol socially. Alcoholics were previously diagnosed by the Psychosocial Care Center - Alcohol and Drugs (CAPS A/D) in the city of Goiania, Goias state, Central Brazil. DNA damage was evaluated by comet assay. The analysis of the rs3813867, rs2031920, and rs2031921 polymorphisms in the promoter region of CYP2E1 gene was performed by Sanger sequencing. Men older than 35 years old were the most common alcoholics. We found increased DNA damage in the case group, compared to the control group (p<0.001). Alcoholics who were heterozygous in the rs3813867, rs2031920, and rs2031921 polymorphisms showed higher DNA damage (tail length and olive tail moment), compared to individuals with the homozygous non-mutated allele. Previous studies have shown that polymorphisms in the promoter region of the CYP2E1 gene could cause higher CYP2E1 transcriptional activity, increasing enzyme activity compared with nondrinkers, indicating that the presence of the mutated allele (heterozygous or homozygous) may be associated with higher alcohol metabolic rates and therefore show increased acetaldehyde levels after alcohol consumption, which then can exert its carcinogenic effect.

Gene specific modifications unravel ethanol and acetaldehyde actions

Ethanol is metabolized into acetaldehyde mainly by the action of alcohol dehydrogenase in the liver, while mainly by the action of catalase in the brain. Aldehyde dehydrogenase-2 metabolizes acetaldehyde into acetate in both organs. Gene specific modifications reviewed here show that an increased liver generation of acetaldehyde (by transduction of a gene coding for a high-activity liver alcohol dehydrogenase ADH1*B2) leads to increased blood acetaldehyde levels and aversion to ethanol in animals. Similarly aversive is an increased acetaldehyde level resulting from the inhibition of liver aldehyde dehydrogenase-2 (ALDH2) synthesis (by an antisense coding gene against aldh2 mRNA). The situation is diametrically different when acetaldehyde is generated in the brain. When the brain ventral tegmental area (VTA) is endowed with an increased ability to generate acetaldehyde (by transfection of liver rADH) the reinforcing effects of ethanol are increased, while a highly specific inhibition of catalase synthesis (by transduction of a shRNA anti catalase mRNA) virtually abolishes the reinforcing effects of ethanol as seen by a complete abolition of ethanol intake in rats bred for generations as high ethanol drinkers. Data shows two divergent effects of increases in acetaldehyde generation: aversive in the periphery but reinforcing in the brain.

Poster 32: Microbial Colonization and Acetaldehyde Production in Oral Cancer and Oral Lichen Planus Lesions

High alcohol consumption and poor oral hygiene are primary risk factors for oral carcinoma. Alcohol consumption leads to increased acetaldehyde levels in saliva due to microbial oxidation of ethanol to acetaldehyde. Acetaldehyde is a highly toxic and carcinogenic product of alcohol fermentation and metabolism in microbes and several studies have linked it to cancers of the upper digestive tract. Acetaldehyde has been classified as a Class I carcinogen in association with alcohol consumption. Acetaldehyde has been found to be able to cause point mutations in DNA, to form DNA adducts and induce gross chromosomal aberrations.

Abstract: P806 EVALUATION OF PROTEIN C HIGHLY SENSITIVE CHILDREN AND ADOLESCENTS IN MUNICIPALITY OF ITAPETININGA-BRAZIL

DNA damage caused by the accumulation of bio-products generated in the biotransformation of ethanol to acetaldehyde mediated by the CYP2E1 enzyme has been studied. To evaluate DNA damage in peripheral blood lymphocytes and the possible association with polymorphisms in the promoter region of the CYP2E1 gene, we performed a case-control study including 75 alcoholics and 59 individuals who consume alcohol socially. Alcoholics were previously diagnosed by the Psychosocial Care Center – Alcohol and Drugs (CAPS A/D) in the city of Goiania, Goias state, Central Brazil. DNA damage was evaluated by comet assay. The analysis of the rs3813867, rs2031920, and rs2031921 polymorphisms in the promoter region of CYP2E1 gene was performed by Sanger sequencing. Men older than 35 years old were the most common alcoholics. We found increased DNA damage in the case group, compared to the control group (p < 0.001). Alcoholics who were heterozygous in the rs3813867, rs2031920, and rs2031921 polymorphisms showed higher DNA damage (tail length and olive tail moment), compared to individuals with the homozygous non-mutated allele. Previous studies have shown that polymorphisms in the promoter region of the CYP2E1 gene could cause higher CYP2E1 transcriptional activity, increasing enzyme activity compared with nondrinkers, indicating that the presence of the mutated allele (heterozygous or homozygous) may be associated with higher alcohol metabolic rates and therefore show increased acetaldehyde levels after alcohol consumption, which then can exert its carcinogenic effect.

Antabuse Reaction With Ceftin

Back to table of contents Previous article Next article Letters to the EditorFull AccessAntabuse Reaction With CeftinJEFFREY A. MATTES M.D.,JEFFREY A. MATTES M.D.Search for more papers by this author,Published Online:1 Nov 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The antibiotic Ceftin is cefuroxime axetil (1) ; the axetil is converted to acetaldehyde (1) . I recently encountered the following disulfiram reaction. A patient receiving Antabuse (disulfiram) (125 mg in the morning for the prior 18 months) with generally good compliance was given Ceftin (cefuroxime) and, within 1 hour after the first oral dose (250 mg at 6 p.m.), developed nausea, vomiting, and stomach cramps. These symptoms lasted 8 to 9 hours; the patient did not take another dose of the Ceftin (he was not rechallenged).This reaction was presumably caused by the accumulation of acetaldehyde (alcohol is converted to acetaldehyde; disulfiram blocks the conversion of acetaldehyde to acetate, and a disulfiram reaction is caused by increased acetaldehyde levels). Odyssey Pharmaceuticals (makers of Antabuse) had no reports of an interaction between Ceftin and Antabuse, but very small amounts of alcohol can cause a disulfiram reaction, so it might be assumed that even smaller amounts of acetaldehyde can do the same.Princeton, N.J.Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.Reference1. Manufacturer’s approved labeling for Ceftin, in Physicians’ Desk Reference. Montvale, NJ, Thomson PDR, 2006, pp 1369–1373Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 163Issue 11 November, 2006Pages 2019-2020THE AMERICAN JOURNAL OF PSYCHIATRY November 2006 Volume 163 Number 11 Metrics PDF download History Published online 1 November 2006 Published in print 1 November 2006

Risk factors in alcohol associated breast cancer: alcohol dehydrogenase polymorphism and estrogens.

Chronic alcohol consumption is associated with an increased risk for breast cancer, even if consumed in moderate doses. Since acetaldehyde is a carcinogenic factor associated with chronic alcohol consumption, individuals with the alcohol dehydrogenase 1C*1 allele (ADH1C*1 allele) seem to be at particular risk, since this allele encodes for a rapidly ethanol metabolizing enzyme leading to increased acetaldehyde levels. Since recent epidemiological studies demonstrated an increased risk for breast cancer for individuals with the ADH1C*1 allele, we have investigated here ADH1C genotypes in moderate alcohol consumers. Furthermore, estradiols are also known risk factors for breast cancer and acute alcohol ingestion in high doses results in increased serum estradiol concentrations. Thus, in the present study, we tested the effect of low ethanol doses on estrogen serum concentrations. We analyzed the ADH1C genotype in 117 moderate alcohol consumers with breast cancer and in 111 age-matched women with alcohol associated diseases without cancer (74 cirrhotics, 22 patients with pancreatitis and 15 alcohol dependent patients). In addition, 107 healthy controls were studied. Genotyping of the ADH1C-locus was performed using polymerase chain reaction-based restriction fragment length polymorphism methods on leukocyte DNA. To study the effects of ethanol on estradiol levels, ethanol in a dose of 0.225 g/kg body weight was given orally to 8 premenopausal women at various time points of their menstrual cycle. Thereafter estradiol serum concentrations were measured over time. The allele frequency of the ADH1C*1 allele was found to be significantly increased in moderate alcohol consumers with breast cancer as compared to age-matched alcoholic controls without cancer (62% vs. 41.9%, p=0.0035). Women with the ADH1C*1,1 genotype were found to be 1.8 times more at risk for breast cancer than those with another genotype (95% CI 1.431-2.330, p<0.001). Oral ethanol increased serum estradiol levels significantly by 27-38%. The data demonstrate that moderate alcohol consumers with the ADH1C*1 allele have an increased risk to develop breast cancer and even small amounts of alcohol increase serum estradiol levels significantly in premenopausal women especially in the midphase of the menstrual cycle.

Acetaldehyde-collagen adducts in N-nitrosodimethylamine-induced liver cirrhosis in rats

Increased acetaldehyde levels have been found in non-alcoholic liver diseases and an acetaldehyde-collagen adduct has been reported in rats with CCl4-induced cirrhosis. In cytosol and microsomes of rats with cirrhosis produced by N-nitrosodimethylamine, a similar acetaldehyde-protein adduct of approximately 200 kD was recognized by rabbit IgG raised against either an in vitro produced hemocyanin-acetaldehyde adduct or an in vivo occurring P4502E1-acetaldehyde adduct isolated from alcohol-fed rats, as well as by anti-rat collagen (I) IgG. Its immune complexes contained 3 proteins that reacted with the anti-collagen IgG and were digested by collagenase: 2 proteins with molecular weights similar to procollagens alpha 1 and alpha 2, and a beta 1,2(I)-like protein which was readily produced by in vitro modification of cytosol with acetaldehyde.

Blood acetaldehyde response to ethanol ingestion during the reproductive cycle of the female rat

Acetaldehyde could mediate a number of the toxic effects of alcohol both in females and their offspring. Thus, we assessed the blood acetaldehyde response to ethanol (3 g/kg) at various stages of the female reproductive cycle. Blood levels were low throughout the various phases of the estrous cycle and during most of pregnancy. By contrast, a 4-fold rise in maternal blood acetaldehyde occurred at the end of pregnancy (day 20), continued to increase during lactation (17-fold at day 14) and returned to non-pregnant values after weaning or after pup removal at birth. Both enhanced rate of ethanol oxidation and decreased activity of the low Km aldehyde dehydrogenase in liver mitochondria contributed to the increased acetaldehyde levels. Acetaldehyde was detectable in fetal blood, but only a small fraction of the high maternal values in pregnancy reached the fetus through the umbilical vein. Chronic alcohol administration resulted in decreased fetal size and striking enlargement of the placenta with possible implications for abnormal fetal development. Thus, the high maternal acetaldehyde levels at the end of pregnancy may exert deleterious effects on many maternal organs, including those (such as placenta) which are required for normal fetal development.

A Study of the Calcium Carbimide‐Ethanol Interaction in Man: Symptom Responses

Oral administration of ethanol up to 24 hr following calcium carbimide (CO. 0.7 mg/kg, produced an increase in blood acetaldehyde level, tachycardia, and increased pulse pressure due mainly to decrease in diastolic blood pressure, with reports of palpitations, shortness of breath, and facial warmth by most subjects. Positive linear correlations existed between acetaldehyde level and physiologic changes and acetaldehyde level and symptom responses, but there was appreciable individual variability in these responses. The magnitude and duration of chemical and physiological changes were greatest for the 4‐hr CC pretreatment interval and the 0.5 g/kg ethanol dose. For the 12‐hr CC pretreatment interval, symptoms were reported for the times of increased acetaldehyde level and as the CC pretreatment interval was shortened, symptom responses were intense but more variable. Symptom response ceased before the acetaldehyde level decreased below 4.0 g/ml and the heart rate declined below 100 beats/min. Symptom responses were significant compared to control for the 0.5 g/kg ethanol dose only. Two of 11 subjects expressed the desire for more ethanol during the 0.5 g/kg ethanol‐12‐hr CC pretreatment interaction. The results are discussed with respect to the clinical use of CC in alcoholism treatment.

Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine.

The blood pressure response after ethanol administration was studied in relation to blood acetaldehyde levels, aldehyde-dehydrogenase (ALDH)--and dopamine-beta-hydroxylase (DBH) activities in rats pretreated with the ethanol-sensitizing compounds disulfiram, cyanamide and coprine and the DBH-inhibitor FLA-57. Disulfiram, cyanamide and coprine, but not FLA-57, inhibited the low-Km ALDH in the liver and caused an increased acetaldehyde level in blood. Disulfiram and FLA-57, but not cyanamide and coprine, decreased the DBH-activity in the heart and the levels of norepinephrine in the heart and the brain. In disulfiram-treated rats with a low DBH-activity, a fall in blood pressure was observed at acetaldehyde levels being slightly higher than those found in control rats. In disulfiram-treated rats with a DBH-activity close to control activity and in rats pretreated with cyanamide or coprine, a fall in blood pressure were observed in rats pretreated with FLA-57. In rats pretreated with coprine + FLA-57, the fall in blood pressure was similar, or even lower, than in rats pretreated with coprine alone. The results suggest that acetaldehyde is the main determinant of the hypotension elicited by ethanol in rats pretreated with ALDH-inhibitors, and that the role of DBH in the disulfiram-ethanol reaction has been over-estimated in previous studies.

Effects of long-term ethanol treatment on aldehyde and alcohol dehydrogenase activities in rat liver

Administration of intoxicating doses of ethanol by gavage for 3 weeks caused weight loss and reduced hepatic aldehyde dehydrogenase activity in the soluble, mitochondrial and microsomal fractions. Rats receiving equivalent amounts of ethanol as a constituent of a liquid diet for 5 weeks gained weight and showed no changes in aldehyde dehydrogenase activity. Alcohol dehydrogenase activity was decreased in the rats treated by gavage and unchanged in those given ethanol in the diet, but in spite of this the rate of ethanol elimination was accelerated in both groups. In the livers of two strains of rats genetically selected for their difference in voluntary alcohol consumption, the mitochondrial and microsomal aldehyde dehydrogenase activities had previously been shown to be significantly higher in the alcohol-consuming (AA) than in the alcohol-avoiding (ANA) rats. Similar differences were now found after long-term intragastric ethanol administration, although in both strains the absolute levels of aldehyde dehydrogenase were reduced. Profound reduction of mitochondrial low- K m aldehyde dehydrogenase activity and high blood acetaldehyde were observed, especially in the ANA rats. This suggests a possible connection between the low activity of this enzyme and the increased acetaldehyde level.