Acetaldehyde

Distribution by Scientific Domains

Terms modified by Acetaldehyde

  • acetaldehyde level

  • Selected Abstracts


    [Commentary] ACETALDEHYDE: A CUMULATIVE CARCINOGEN IN HUMANS

    ADDICTION, Issue 4 2009
    MIKKO SALASPURO
    No abstract is available for this article. [source]


    Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007
    Sangsu Bang
    Abstract Six transient receptor potential (TRP) ion channels expressed in the sensory afferents play an important role as body thermosensors and also as peripheral pain detectors. It is known that a number of natural compounds specifically activate those sensory neuronal TRP channels, and a well-known example is cinnamaldehyde for TRPA1. Here we show that human and mouse TRPA1 are activated by acetaldehyde, an intermediate substance of ethanol metabolism, in the HEK293T cell heterologous expression system and in cultured mouse trigeminal neurons. Acetaldehyde failed to activate other temperature-sensitive TRP channels expressed in sensory neurons. TRPA1 antagonists camphor and gadolinium, and a general TRP blocker ruthenium red inhibited TRPA1 activation by acetaldehyde. Camphor, gadolinium and ruthenium red also suppressed the acute nociceptive behaviors induced by the intradermal administration of acetaldehyde into the mouse footpads. Intradermal co-application of prostaglandin E2 and acetaldehyde greatly potentiated the acetaldehyde-induced nociceptive responses, and this effect was reversed by treatment with the TRPA1 antagonist camphor. These results suggest that acetaldehyde causes nociception via TRPA1 activation. Our data may also help elucidate the mechanisms underlying acetaldehyde-related pathological symptoms such as hangover pain. [source]


    Stereochemistry of the Conversion of 2-Phenoxyethanol into Phenol and Acetaldehyde by Acetobacterium sp.

    HELVETICA CHIMICA ACTA, Issue 7 2003
    Giovanna Speranza
    The conversion of 2-phenoxyethanol to phenol and acetate by the anaerobic bacterium Acetobacterium sp. strain LuPhet1 proceeds through acetaldehyde with concomitant migration of a H-atom from C(1) to C(2) of the glycolic moiety. Separate feeding experiments with (R)- and (S)-2-phenoxy(1- 2H)ethanol, prepared via chemoenzymatic syntheses, indicate that the H-atom involved in the 1,2-shift is the pro-S one of the enantiotopic couple of the alcohol function. [source]


    Breath gas aldehydes as biomarkers of lung cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 11 2010
    Patricia Fuchs
    Abstract There is experimental evidence that volatile substances in human breath can reflect presence of neoplasma. Volatile aldehydes were determined in exhaled breath of 12 lung cancer patients, 12 smokers and 12 healthy volunteers. Alveolar breath samples were collected under control of expired CO2. Reactive aldehydes were transformed into stable oximes by means of on-fiber-derivatization (SPME-OFD). Aldehyde concentrations in the ppt and ppb level were determined by means of gas chromatography-mass spectrometry (GC-MS). Exhaled concentrations were corrected for inspired values. Exhaled C1,C10 aldehydes could be detected in all healthy volunteers, smokers and lung cancer patients. Concentrations ranged from 7 pmol/l (161 pptV) for butanal to 71 nmol/l (1,582 ppbV) for formaldehyde. Highest inspired concentrations were found for formaldehyde and acetaldehyde (0,55 nmol/l and 0,13 nmol/l, respectively). Acetaldehyde, propanal, butanal, heptanal and decanal concentrations showed no significant differences for cancer patients, smokers and healthy volunteers. Exhaled pentanal, hexanal, octanal and nonanal concentrations were significantly higher in lung cancer patients than in smokers and healthy controls (ppentanal = 0.001; phexanal = 0.006; poctanal = 0.014; pnonanal = 0.025). Sensitivity and specificity of this method were comparable to the diagnostic certitude of conventional serum markers and CT imaging. Lung cancer patients could be identified by means of exhaled pentanal, hexanal, octanal and nonanal concentrations. Exhaled aldehydes reflect aspects of oxidative stress and tumor-specific tissue composition and metabolism. Noninvasive recognition of lung malignancies may be realized if analytical skills, biochemical knowledge and medical expertise are combined into a joint effort. [source]


    Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinking

    JOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007
    M. I. Díaz Gómez
    Abstract Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury. Copyright © 2007 John Wiley & Sons, Ltd. [source]


    FRUIT BRANDY PRODUCTION BY BATCH COLUMN DISTILLATION WITH REFLUX

    JOURNAL OF FOOD PROCESS ENGINEERING, Issue 1 2005
    MICHAEL J. CLAUS
    ABSTRACT The relationship between the operating parameters of batch fruit spirits column stills with reflux and the congener (trace compounds that provide flavors and aromas) concentrations in resulting fruit spirits has not been widely studied. Congener concentrations were determined in three different collection fractions, or "cuts," during batch distillation. Acetaldehyde and ethyl acetate were found in higher concentrations in the head cut, first overhead fraction, of the distillation and have lower boiling points relative to ethanol. 1-Propanol and isoamyl alcohol (isopentanol) were present in higher concentrations in the tail cut, third or final fraction, of the distillation and have boiling points that are higher than ethanol. Methanol has a unique concentration profile as it has higher concentrations in both the head and tail cuts, but a lower concentration in the heart cut, the middle fraction which is the desired product of the distillation. Methanol was of particular interest because the distillate must adhere to governmental regulations that limit its concentration in the product. Operating-condition parameters that were studied include the number of trays used in the distillation as well as the use of a "catalytic converter," a high surface, copper-packing material thought to catalyze formation of cyanide-containing compounds allowing them to be separated from the distillate. The effect of the number of trays used in a distillation on the concentration of ethanol and the congeners, methanol, acetaldehyde, ethyl acetate, 1-propanol and isoamyl alcohol in the final distilled spirits product is presented. An additional result of acetaldehyde production at the copper surface of the catalytic converter was also discovered in the analysis of the data. [source]


    Formation of Malonaldehyde, Formaldehyde, and Acetaldehyde in Apple Juice Induced by Ionizing Radiation

    JOURNAL OF FOOD SCIENCE, Issue 7 2002
    X. Fan And
    ABSTRACT: We investigated the effects of ionizing radiation on the formation of malonaldehyde (MA), formaldehyde (FA), and acetaldehyde (ACT) in apple juice. The formation of MA, FA, and ACT in both pasteurized and fresh juice increased with radiation dose. The G values (number of species formed per 100 eV absorbed) for MA, FA, and ACT in pasteurized juice were 0.0056, 0.061, and 0.044, respectively. MA concentration decreased rapidly during storage at 5°C, while ACT and FA did not. Irradiation-induced formation of MA, FA, and ACT decreased with decreasing irradiation temperature. Exclusion of oxygen during irradiation reduced formation of ACT and FA, but not MA. Adding 1000 ppm of ascorbate, sorbate, or sulfite to juice before irradiation also decreased MA formation. [source]


    Ethanol Modulates Corticotropin Releasing Hormone Release From the Rat Hypothalamus: Does Acetaldehyde Play a Role?

    ALCOHOLISM, Issue 4 2010
    Carla Cannizzaro
    Background and Methods:, Ethanol (EtOH) activates hypothalamic,pituitary,adrenal (HPA) axis, resulting in adrenocorticotropin hormone, glucocorticoid release, and in modifications of the response of the axis to other stressors. The initial site of EtOH action within the HPA system seems to be the hypothalamus. Thus, to determine the mechanisms responsible for these effects, we investigated: (i) whether EtOH was able to release corticotrophic releasing hormone (CRH) from incubated hypothalamic explants; (ii) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in EtOH activity. To this aim, rat hypothalamic explants were incubated with: (i) medium containing EtOH at 32.6 × 103 ,M; (ii) different concentration of ACD (1, 3, 10, and 30 ,M); (iii) EtOH plus 3amino-1,2,4-triazole (3AT, 32 × 103 ,M) an inhibitor of cerebral catalase; (iv) ACD plus D-penicillamine (DP, 50.3 × 103 ,M) an ACD-trapping agent. CRH levels were evaluated by a radioimmunoassay. Results:, Incubation with EtOH induced a 7-fold increase in CRH secretion, with respect to basal levels; ACD was able to stimulate CRH release in a dose-dependent manner; the inhibition of cerebral catalase by 3AT blocked EtOH-induced CRH outflow; the inactivation of ACD by DP reverted the ACD-stimulating effect on CRH secretion. Conclusions:, These data show that both EtOH and acetaldehyde are able to increase hypothalamic CRH release from the rat hypothalamus and that acetaldehyde itself appears to be the mediator of EtOH activity. [source]


    Role of Dopamine D1 Receptors and Extracellular Signal Regulated Kinase in the Motivational Properties of Acetaldehyde as Assessed by Place Preference Conditioning

    ALCOHOLISM, Issue 4 2010
    Liliana Spina
    Background:, The role of dopamine D1 receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place-conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place-conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D1 receptors and ERK activation in acetaldehyde-elicited place preference has not been determined. The aim of this study was to assess the role of D1 receptors blockade and MEK inhibition in the acquisition of acetaldehyde-elicited conditioned place preference. Methods:, Male Sprague,Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg/kg i.g.) or ethanol (1 g/kg i.g.) administration. The D1 receptor antagonist, SCH 39166 (50 ,g/kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde-elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 ,g i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)-elicited place preference. Results:, Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose (30 and 90 but not 1 ,g i.c.v.) and time (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde- and significantly reduced the acquisition of morphine-elicited conditioned place preference. Conclusions:, These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D1 receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde-elicited conditioned place preference highlights the importance of the D1 receptor,ERK pathway in its motivational effects. [source]


    Acetaldehyde and the Hypothermic Effects of Ethanol in Mice

    ALCOHOLISM, Issue 11 2009
    Catherine Closon
    Background:, Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of acetaldehyde or the contribution of acetaldehyde to ethanol-induced hypothermia. The aim of the present study is to better understand the hypothermic effects of acetaldehyde and the possible contribution of acetaldehyde in ethanol-induced hypothermia, especially under conditions leading to acetaldehyde accumulation. Methods:, Female Swiss mice were injected intraperitoneally with ethanol and acetaldehyde and their rectal temperatures were measured with a digital thermometer at various time points after the injections. Experiment 1 compared the hypothermic effects of various acetaldehyde doses (0 to 300 mg/kg) with a reference dose of ethanol (3 g/kg). Experiment 2 tested the effects of a pretreatment with the aldehyde dehydrogenase (ALDH) inhibitor cyanamide (25 mg/kg) on ethanol- and acetaldehyde-induced hypothermia. In experiments 3 and 4, mice received a combined pretreatment with cyanamide and the alcohol dehydrogenase (ADH) inhibitor 4-Methylpyrazole (10 mg/kg) before the injection of ethanol or acetaldehyde. Results:, Acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but of shorter duration than ethanol-induced hypothermia. The inhibition of ALDH enzymes by cyanamide induced a strong potentiation of both ethanol- and acetaldehyde-induced hypothermia. The pretreatment with 4-MP prevented the potentiation of ethanol-induced hypothermia by cyanamide, but slightly increased the potentiation of acetaldehyde-induced hypothermia by cyanamide. Conclusions:, The results of the present study clearly show that acetaldehyde has hypothermic properties in mice at least at relatively high concentrations. Furthermore, the accumulation of acetaldehyde following ALDH inhibition strongly enhanced the hypothermic effects of ethanol. These latter results confirm the hypothermic properties of acetaldehyde and show that acetate, the next step in ethanol metabolism, is not involved in these hypothermic effects. Finally, the experiment with 4-MP indicates that the potentiating effects of cyanamide are mediated by the peripheral accumulation of acetaldehyde, which then reaches the brain to induce a severe hypothermia. [source]


    IgA Immune Responses Against Acetaldehyde Adducts and Biomarkers of Alcohol Consumption in Patients with IgA Glomerulonephritis

    ALCOHOLISM, Issue 7 2009
    Kati Kaartinen
    Background:, The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined. Methods:, A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self-reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT), glutamyl transferase, ,-CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde,protein adducts. Results:, In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and , -CDT, p < 0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake. Conclusions:, These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted. [source]


    Reduction of Ethanol-Derived Acetaldehyde Induced Motivational Properties by l -Cysteine

    ALCOHOLISM, Issue 1 2009
    Alessandra T. Peana
    Background:, Experimental evidences suggest that acetaldehyde (ACD) contributes to the positive motivational properties of ethanol (EtOH) as assessed by the place conditioning paradigm; indeed, we found that by reducing ACD production and/or by using ACD-sequestrating agents, EtOH is deprived from its motivational properties. Thiol products, such as the amino acid cysteine, are known to be effective ACD-sequestering agents. Cysteine is able to covalently bind ACD thereby forming a stable, nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, we treated rats with l -cysteine before intragastric administration of EtOH or ACD. Methods:, Male Wistar rats were pretreated intraperitoneally with saline or l -cysteine (10, 20, or 30 mg/kg), before intragastric administration of saline, EtOH (1 g/kg), or ACD (20 mg/kg). The specificity of l -cysteine effect was addressed using morphine-induced conditioned place preference (cpp) (2.5 mg/kg, i.p.). Results:,l -cysteine dose-dependently prevented both EtOH and ACD-induced cpp but did not interfere with morphine-induced cpp, suggesting that l -cysteine specifically modulates the motivational properties of EtOH. Conclusion:, The present results further underscore the role of EtOH-derived ACD in EtOH-induced motivational properties. l -cysteine, by binding EtOH-derived ACD, would deprive it of its rewarding properties and reduce its abuse liability. [source]


    Salivary Acetaldehyde Concentration According to Alcoholic Beverage Consumed and Aldehyde Dehydrogenase-2 Genotype

    ALCOHOLISM, Issue 9 2008
    Akira Yokoyama
    Background:, Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers. Methods:, In a randomized cross-over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3-week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking. Results:, The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 ,M in saliva vs. 2 to 5 ,M in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 ,M in saliva vs. 12 to 25 ,M in blood), and they were 13 to 25 ,M higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes. Conclusions:, There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype. [source]


    Key Role of Ethanol-Derived Acetaldehyde in the Motivational Properties Induced by Intragastric Ethanol: A Conditioned Place Preference Study in the Rat

    ALCOHOLISM, Issue 2 2008
    Alessandra T. Peana
    Background:, Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. In spite of the aversive properties classically ascribed to ACD, it has recently been suggested that ACD might mediate some of the motivational effects of EtOH. Accordingly, the relative role of ACD in the positive motivational properties of EtOH ingested is increasingly becoming the matter of debate. Thus, we studied the ability of intragastrically administered EtOH, ACD and EtOH-derived ACD to induce conditioned place preference (cpp) in rats. Methods:, Wistar rats were pretreated intraperitoneally with saline, the peripheral competitive inhibitor of ADH, 4-methylpyrazole (4-MP, 22.5, 45 or 67.5 mg/kg) or with the selective ACD-sequestrating agent, d -penicillamine (DP, 25 or 50 mg/kg), before the intragastric administration of saline, EtOH (0.5, 1 or 2 g/kg) or ACD (10, 20, or 40 mg/kg). The specificity of 4-MP and DP effects was addressed using morphine-induced cpp (2.5 mg/kg). Results:, Both, EtOH and ACD dose-dependently induced cpp; further, while EtOH-induced cpp was prevented by the administration of 4-MP and by DP, ACD-induced cpp was unaltered by 4-MP administration and prevented by DP. Both pretreatments did not interfere with morphine-induced cpp indicating that 4-MP and DP specifically modulate the motivational properties of EtOH and ACD. Conclusion:, The ability of 4-MP and DP to decrease EtOH-induced cpp suggests that a reduction of ACD levels is crucial in depriving EtOH from its motivational properties as indexed by the cpp procedure. In addition, this conclusion is supported by the inefficacy of 4-MP in preventing ACD-induced cpp, and by its blockade observed after administration of the selective ACD sequestrating agent DP. The present results underscore the role of EtOH-derived ACD in EtOH-induced motivational properties as well as its abuse liability. [source]


    Evaluation of the Effect of Ethanol's Toxic Metabolite Acetaldehyde on the Gastrointestinal Oligopeptide Transporter, PEPT1: In Vitro and in Vivo Studies

    ALCOHOLISM, Issue 1 2008
    Scott J. Fisher
    Background:, The effects of alcohol consumption and its subsequent metabolism on drug transport, absorption and pharmacokinetics are poorly understood. This study examines the effects of the ethanol metabolite, acetaldehyde, on the clinically relevant drug transporter, PEPT1. The metabolism of ethanol and the following acetaldehyde formation is thought to modulate the uptake capacity of PEPT1 within the gastrointestinal tract for a variety of clinically important peptidomimetic drug compounds. Methods:, Glycylsarcosine ([3H]-GlySar), a nonhydrolysable PEPT1 specific substrate was used in our studies. In vitro uptake studies were performed in the Caco-2 and Chinese hamster ovary (CHO)-hPEPT1 cell models, measuring cellular uptake of labeled compound against increasing levels of unlabeled compound in the presence of acetaldehyde. In vivo absorption of [3H]-GlySar was measured in male Sprague,Dawley rats that were treated with oral dose of ethanol/disulfiram (5 g/kg / 100 mg/kg) for 6 days. These results were compared to control rats treated with saline, ethanol alone or disulfiram alone. Results:, In vitro uptake of [3H]-GlySar in CHO-hPEPT1 cells treated with 1 mM acetaldehyde was significantly decreased (p < 0.05) as compared to untreated controls. The uptake of [3H]-GlySar in Caco-2 cell monolayers treated with 1 mM acetaldehyde was also significantly decreased as compared to the untreated control cells. In vivo absorption of [3H]-GlySar in ethanol treated rats, as measured by AUC0,12 hours were decreased by approximately 50% versus the control rat group. Conclusion:, The effects of acetaldehyde due to consumption of ethanol on the uptake and bioavailability of therapeutic drug compounds transported by the PEPT1 oligopeptide transporter have not been documented. In the present studies, we demonstrate that acetaldehyde significantly modulates PEPT1 function and, thereby, affects drug bioavailability. To our best knowledge, this is the first report on the effects of an ethanol metabolite on substrate absorption in the gastrointestinal tract, rather than interactions in the liver, which is an under-represented area of research in alcohol pathophysiology. [source]


    Michaelis-Menten Elimination Kinetics of Acetaldehyde During Ethanol Oxidation

    ALCOHOLISM, Issue 2002
    Tatsuya Fujimiya
    Background Acetaldehyde (AcH) is a toxic metabolite of ethanol (EtOH). The pharmacokinetics of blood AcH during EtOH oxidation was studied with or without the administration of aldehyde dehydrogenase 2 inhibitor (cyanamide) in rabbits. Methods An bolus of EtOH saline solution (0.25, 0.5, 1.0, 1.5, and 2.0 g/kg) was injected intravenously. Cyanamide was administered intraperitoneally (25 mg/kg body weight) to the cyanamide-treated group. Blood EtOH and AcH concentrations were measured by using head-space gas chromatography. Results In the control group, the first peak of the blood AcH appeared immediately and the second elevation appeared 1 to 4 hr after administration at a high EtOH dose. The blood AcH levels other than the second elevation part were significantly correlated to the blood EtOH levels. In the cyanamide-treated group, a peak and a plateau formed at the time corresponding to the second peak in the control group. The peak and plateau concentration of AcH increased markedly. We attempted simultaneous curve fitting, using the five blood EtOH and AcH concentration-time curves, to determine the pharmacokinetic model. Consequently, the AcH elimination was best described by a Michaelis-Menten kinetic model in both groups. Conclusions The blood AcH profile was suggested to consist of the first and second components that are related to the blood EtOH concentration itself and the metabolic formation of AcH, respectively. With higher EtOH doses or aldehyde dehydrogenase 2 inhibition, the second component becomes prominent as a result of the capacity-limited property of the metabolism of AcH, which is described by Michaelis-Menten elimination kinetics. [source]


    Role of Acetaldehyde in the Discriminative Stimulus Effects of Ethanol

    ALCOHOLISM, Issue 6 2002
    Etienne Quertemont
    Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol-induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear. Methods: The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two-lever drug discrimination paradigm with food reinforcement. Male Long-Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0,2.5 g/kg by gavage) and acetaldehyde (0,300 mg/kg intraperitoneally). A cumulative dose-response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination. Results: Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose-response curves for ethanol discrimination. Conclusions: These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose-response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol. [source]


    Involvement of Acetaldehyde in Alcohol Addiction

    ALCOHOLISM, Issue 1 2002
    William J. McBride
    This article presents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers and chairs were William J. McBride and Ting-Kai Li. The presentations were (1) Metabolism of ethanol in the brain and the behavioral consequences, by Richard A. Deitrich and Sergey Zimatkin; (2) Catalase production of acetaldehyde as a possible mediator of the psychopharmacological effects of ethanol, by Brian R. Smith; (3) The reinforcing actions of acetaldehyde in the ventral tegmental area, by Zachary A. Rodd-Henricks; and (4) Salsolinol and alcohol addiction, by William J. McBride. [source]


    Metronidazole Increases Intracolonic but Not Peripheral Blood Acetaldehyde in Chronic Ethanol-Treated Rats

    ALCOHOLISM, Issue 4 2000
    Jyrki Tillonen
    Background: Metronidazole leads to the overgrowth of aerobic flora in the large intestine by reducing the number of anaerobes. According to our previous studies, this shift may increase intracolonic bacterial acetaldehyde formation if ethanol is present. Metronidazole is also reported to cause disulfiram-like effects after alcohol intake, although the mechanism behind this is obscure. Therefore, the aim was to study the effect of long-term metronidazole and alcohol treatment on intracolonic acetaldehyde levels and to explore the possible role of intestinal bacteria in the metronidazole related disulfiram-like reaction. Methods: A total of 32 rats were divided into four groups: controls (n= 6), controls receiving metronidazole (n= 6), ethanol group (n= 10), and ethanol and metronidazole group (n= 10). All rats were pair-fed with the liquid diet for 6-weeks, whereafter blood and intracolonic acetaldehyde levels and liver and colonic mucosal alcohol (ADH) and aldehyde dehydrogenase (ALDH) activities were analyzed. Results: The rats receiving ethanol and metronidazole had five times higher intracolonic acetaldehyde levels than the rats receiving only ethanol (431.4 ± 163.5 ,M vs. 84.7 ± 14.4 ,M, p= 0.0035). In contrast, blood acetaldehyde levels were equal. Cecal cultures showed the increased growth of Enterobacteriaceae in the metronidazole groups. Metronidazole had no inhibitory effect on hepatic or colonic mucosal ADH and ALDH activities. Conclusions: The increase in intracolonic acetaldehyde after metronidazole treatment is probably due to the replacement of intestinal anaerobes by ADH-containing aerobes. Unlike disulfiram, metronidazole neither inhibits liver ALDH nor increases blood acetaldehyde. Thus, our findings suggested that the mechanism behind metronidazole related disulfiram-like reaction might be located in the gut flora instead of the liver. [source]


    Accumulation of Hemoglobin-Associated Acetaldehyde With Habitual Alcohol Drinking in the Atypical ALDH Genotype

    ALCOHOLISM, Issue 1 2000
    Tatsuya Takeshita
    Background: Those with the atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have high blood concentrations of free acetaldehyde, an active metabolite of ethanol, after drinking alcohol. In the present study, we measured acetaldehyde reversibly bound to hemoglobin (HbAA) in Japanese male workers. Methods: One hundred and sixty Japanese male workers in one plant participated with informed consent. The subjects were genotyped for the ALDH2 polymorphism by polymerase chain reaction method. HbAA levels were measured using a high performance liquid chromatography system with a fluorescence detector. For the study in which we examined accumulation of HbAA, eight Asian male volunteers participated with informed consent. Results: Although HbAA levels were significantly correlated with recent alcohol consumption in both typical (ALDH2*1/*1) and atypical (ALDH2*1/*2)genotypes, the slope in ALDH2*1/*2 was significantly steeper than that in ALDH2*1/*1. Multiple regression analysis on relevant factors for HbAA revealed that not only recent but also daily alcohol consumption increased HbAA levels in those with the ALDH2*1/*2 genotype, which suggests that HbAA accumulates with habitual drinking. We measured HbAA levels before, during, and after alcohol consumption,one drink (0.4 ml/kg) per day,for 7 consecutive days in male volunteers. During the drinking period, HbAA lincarly increased in ALDH2*1/*2 (n= 4) but not in ALDH2*1/*1 (n= 4). After reaching peak levels (+76.1 nmol/g hemoglobin) following the seventh drink, HbAA levels gradually decreased but were significantly higher for 3 days after drinking was discontinued. Conclusions: We demonstrated that HbAA levels accumulate with habitual alcohol drinking in the atypical ALDH2 genotype. HbAA was shown to be a good biomarker for increased internal exposure levels to acetaldehyde. [source]


    Effect of fat replacers on kefir quality

    JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 4 2010
    Bilge Ertekin
    Abstract The purpose of the study was to determine the effects of fat replacers on the quality of non-fat kefir. Skim milk fortified with Dairy Lo® (DL) and inulin (INU) was fermented with kefir grains to manufacture kefir. The results of compositional, microbiological, rheological and sensorial analyses were compared with whole kefir (WK) and non-fat kefir (NFK) controls. Results for dry matter, pH and lactic acid ranged between 82.4 and 109.1 g kg,1, 4.26 and 4.40, and 7.0 and 9.2 g L,1, respectively. Acetaldehyde and ethanol contents of samples were between 2.89 and 7.28 mg L,1, and 151.46 and 323.89 mg L,1, respectively. In all samples, Lactobacillus spp., Streptococcus spp. and yeast counts were between 9.1 and 9.9, 9.3 and 9.9, and 5.2 and 5.6 log cfu mL,1, respectively. Kefir samples had non-Newtonian behaviour and pseudoplastic fluid with thixotropy. At the first day, DL had the highest apparent viscosity (3.119 Pa s) while NFK had the lowest value (1.830 Pa s). In the sensory evaluation, odour and taste scores of samples were not different. Dairy Lo® and inulin could be used without any adverse effect for the production of non-fat kefir. Copyright © 2009 Society of Chemical Industry [source]


    Sensory neuropeptides are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigs

    AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2001
    S. Myou
    1,Alcohol-induced asthma is characterized by worsening of asthmatic symptoms after alcohol ingestion. Acetaldehyde, a metabolite of ethanol, is thought to be a main factor of alcohol-induced asthma. Although airway sensory nerves are known to be activated in asthma, there have been no studies investigating the role of tachykinins in the airway response to acetaldehyde. The purpose of the present study was to evaluate the involvement of tachykinins on acetaldehyde-induced bronchoconstriction in guinea-pigs. 2,After capsaicin desensitization or intravenous administration of 10 mg kg,1 FK224, a NK1 and NK2 dual antagonist, airway responses to ascending doses (2.5,20 mg ml,1) of inhaled acetaldehyde was examined using a modified Konzett,Rössler method in guinea-pigs. 3,Inhalation of acetaldehyde induced bronchoconstriction in a dose-dependent manner. The FK224 failed to reduce the acetaldehyde-induced bronchoconstriction. Pretreatment with capsaicin did not alter the bronchoconstriction induced by acetaldehyde at a dose of 2.5,10 mg ml,1. Pretreatment with capsaicin slightly, but significantly, inhibited bronchoconstriction induced by 20 mg ml,1 of acetaldehyde. 4,The present results suggest that tachykinins are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigs. [source]


    Oxidation of Acetaldehyde and Propionaldehyde on a VOx/TiO2 Catalyst in the Presence of Water Vapor

    CHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 11 2006
    W. Ya.
    Abstract The partial oxidation of acetaldehyde and propionaldehyde on a TiO2 supported VOx catalyst in the presence of water vapor was investigated at temperatures from 120 to 280,°C. Depending on the kind of aldehyde and reaction temperature, the selective oxidation to the appropriate carboxylic acid and an oxidative splitting to lower carboxylic acids took place. Acetaldehyde was oxidized to acetic acid with selectivities up to 82,% at ,,200,°C whereas propionic acid was formed only with selectivities of about 20,% at ,,140,°C in the oxidation of propionaldehyde. The oxidative cleavage of propionaldehyde led to the formation of more acetic acid than formic acid, which was in agreement with the higher formation of COx compared to that in the acetaldehyde oxidation. The presence of water and the increasing concentration of oxygen in the feed was found to enhance the selectivity towards the formation of C1 to C3 carboxylic acids by inhibiting the total oxidation of aldehydes and carboxylic acids. [source]


    ChemInform Abstract: Enzymatic Synthesis of Pyruvic Acid from Acetaldehyde and Carbon Dioxide.

    CHEMINFORM, Issue 2 2002
    Masaya Miyazaki
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


    Voltammetric Determination of Free and Total Sulfur Dioxide in Beer

    ELECTROANALYSIS, Issue 5-6 2003
    J. Almeida
    Abstract A voltammetric method for the determination of free and total sulfur dioxide in beer is described. First, volatile aldehydes (mainly acetaldehyde) are purged with nitrogen from a beer sample diluted in alkaline medium, collected in an appropriate electrolyte trapping solution and determined, after derivatization with hydrazine, by voltammetry using a hanging mercury drop electrode. Then, the remaining beer solution is strongly acidified and (total) sulfur dioxide is purged with nitrogen, collected in an appropriate electrolyte trapping solution and determined by voltammetry. The free sulfur dioxide concentration is calculated by difference between (total) sulfur dioxide and acetaldehyde concentrations. The proposed method has a relative standard deviation of about 2.1% and 4.4%, respectively for (total) sulfur dioxide and free sulfur dioxide concentrations normally found in beer, and results are in good agreement with those obtained by the p -rosaniline reference method. [source]


    Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism

    ADDICTION, Issue 4 2009
    Dirk W. Lachenmeier
    ABSTRACT Aims In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. Methods The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose,response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. Results The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10 000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. Conclusions The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10 000 and 1 : 1 000 000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive. [source]


    Identification and quantification of in vitro adduct formation between protein reactive xenobiotics and a lysine-containing model peptide

    ENVIRONMENTAL TOXICOLOGY, Issue 1 2003
    Peter Reichardt
    Abstract Formation of in vitro adducts between different classes of xenobiotics and the lysine-containing peptide Lys-Tyr was monitored by high-performance liquid chromatography and electrospray ionization mass spectrometry. The molecular structures of the main resulting products could be sensitively analyzed by mass spectrometry (flow injection analysis), enabling the detection of characteristic binding formations. Aldehydes such as formaldehyde, acetaldehyde, and benzaldehyde were shown to form stable linkages to lysine amino groups via Schiff bases. Other electrophilic substances (e.g., toluene-2,4-diisocyanate, 2,4-dinitro-1-fluorobenzene, 2,4,6-trinitrobenzene sulfonic acid, dansyl chloride, and phthalic acid anhydride) also formed covalent adducts with lysine residues. The reactivity of the compounds was quantified by measuring the amount of peptide that remained unchanged after incubation for a certain period with the xenobiotic. Although reactivity levels within this group of aldehydes varied only to a small extent, as would be expected, extreme differences were seen among the structurally heterogeneous group of nonaldehyde xenobiotics. These results support the hypothesis that simple chemical reactions may lead to the adduction of nucleophilic macromolecules such as peptides or proteins. Such reactions, in particular, Schiff base formation of aldehydes, have previously been shown to be capable of specifically interfering with costimulatory signaling on T cells. Our results suggest that electrophilic xenobiotics of other classes may also inherit the capacity to exert similar effects. Forming covalent linkage to peptides may represent a possible molecular mechanism of electrophilic xenobiotics in vivo, yielding immunotoxic effects. The model utilized in this study is appropriate for monitoring the adduction of xenobiotics to basic peptides and for analyzing the resulting molecular structures. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 29,36, 2003. [source]


    Alcoholic macrocytosis,is there a role for acetaldehyde and adducts?

    ADDICTION BIOLOGY, Issue 1 2004
    Onni Niemelä
    Although alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions have remained poorly defined. Elevated mean corpuscular volume (MCV), macrocytosis, is the most typical morphological abnormality induced by excessive ethanol consumption. This paper reviews recent data indicating that acetaldehyde, the first metabolite of ethanol, may play a role in the haematological derangements in peripheral blood cells and in bone marrow of alcoholic patients. Studies in experimental animals and in human alcoholics have shown that acetaldehyde can bind to proteins and cellular constituents forming stable adducts. Elevated adduct levels have been found from the erythrocytes of alcohol abusers, which may also be associated with ethanol-induced effects in haematopoiesis and adverse consequences in cellular functions. [source]


    Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats

    ADDICTION BIOLOGY, Issue 4 2003
    María elena Quintanilla
    Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose-response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity. [source]


    Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2001
    V. R. Preedy
    Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, , -tocopherol status is poor in myopathic alcoholics. Reduced , -tocopherol may pre-dispose the muscle to metabolic injury. However, experimental , -tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired , -tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover. [source]