Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Acetaldehyde”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1987

Covalent binding of acetaldehyde to proteins: participation of lysine residues.

The results of this study demonstrate that lysine is the major amino acid participating in the binding of acetaldehyde to proteins. The formation of both stable and unstable acetaldehyde-albumin adducts was shown to occur via the reaction of acetaldehyde with lysine residues. This conclusion was based on the following experimental evidence: (a) the ratio of stable to unstable adducts of bovine serum albumin was similar to that observed for polylysine; (b) acetylation of albumin markedly reduced acetaldehyde binding; (c) the radio-activity profiles (obtained by high-performance liquid chromatographic analysis) of [14C]acetaldehyde modified amino acids hydrolyzed from total and stable adducts of albumin were nearly identical to those of polylysine or alpha-t-boc-lysine. Analysis of stable adducts of albumin indicated two major modified lysine residues; one residue was much more acidic and the other more basic than unmodified lysine. Unstable adducts were shown to be Schiff bases since NaBH4 treatment resulted in the formation of N-ethyllysine residues. The reducing agents, NaCNBH3 and ascorbic acid, both increased stable adduct formation via increased binding to lysine residues; however, a different elution profile of modified lysine residues was observed for these reducing agents. NaCNBH3 increased the formation of N-ethyllysine residues exclusively, whereas ascorbate increased the formation of the acidic adduct of lysine and also caused the formation of an additional modified lysine residue which was present only in the ascorbate-treated polypeptides. In addition to their detection by radioactivity measurements, the acetaldehyde-lysine adducts could also be detected by the fluorescence of their ophthalaldehyde derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1995

Mechanisms of acetaldehyde-mediated growth inhibition: delayed cell cycle progression and induction of apoptosis.

Chronic ethanol exposure has been associated with pleiotropic effects on cellular function in vivo and in vitro, including inhibition of growth. To date, it has been difficult to dissociate the primary effects of ethanol from the effects of ethanol metabolism, generation of acetaldehyde, and reducing equivalents. We have previously described the development of a Chinese hamster ovary cell line, A-10, which expresses a transfected murine-liver alcohol dehydrogenase. Cultures of these cells accumulate acetaldehyde due to the low level of aldehyde dehydrogenase. One noticeable effect of chronic acetaldehyde exposure, but not ethanol exposure, is the inhibition of cell growth. This study focuses on the mechanisms that underlie this growth inhibition. Our studies with the A-10 cell on the rates of [3H]thymidine incorporation and flow cytometry of asynchronous cultures indicated that acetaldehyde did not lead to arrest of the cell cycle in the G1 phase as has been found in other models of ethanol exposure. Rather, we observed a generalized delay in cell cycle progression. However, the slower cell cycle did not account exclusively for the slower rates of cell accumulation. Chronic exposure to acetaldehyde also increased the rate of cell death. The increased rate of cell death was both cumulative and dose-dependent. The dead cells accumulated in the medium and were apoptotic. Apoptosis was confirmed using morphological criteria and quantitation of DNA fragmentation. These data lend additional support to the idea that chronic acetaldehyde exposure can affect the mechanisms that regulate cell division and the apoptotic program.

Acetaldehyde↗
PubMed1996

Relationship between alcohol intake and immunoglobulin a immunoreactivity with acetaldehyde-modified bovine serum albumin.

Acetaldehyde, the main metabolite of ethanol, is a highly reactive species that reacts with macromolecules to produce unstable and stable adducts. Acetaldehyde-modified proteins are immunogenic and have been detected in the liver and blood of alcoholics. Furthermore, antibodies reactive with acetaldehyde-modified proteins have been detected in the plasma of social drinkers and alcoholics. However, the class distribution of immunoglobulins reactive with modified proteins was different in the two groups, being predominantly immunoglobulin (Ig)M in social drinkers, but IgM and IgA in alcoholics. In this study, we demonstrate that heavy drinkers (alcohol intake > 130 g/week for females and 150 g/week for males) also exhibit IgA reactivity with acetaldehyde-modified proteins. The IgA adduct-specific reactivity (IgA reactivity with acetaldehyde-modified bovine serum albumin-reactivity with native bovine serum albumin) showed a moderate correlation with self-reported alcohol intake, but did not correlate with markers such as plasma transaminase, gamma-glutamyltransferase activity, or mean corpuscular volume. IgA adduct-specific reactivity had similar specificity to the conventional tests of alcohol abuse, but had higher sensitivity than the other tests, especially with heavy drinkers. Data presented herein demonstrate that elevated IgA reactivity with acetaldehyde-modified epitopes is associated with heavy drinking and is a potential marker for high alcohol intake.

Acetaldehyde↗
PubMed1992

Clinical responses in relation to blood acetaldehyde levels.

A study was undertaken to examine the relationship between blood acetaldehyde levels and clinical responses in volunteers receiving the anti-alcohol drugs disulfiram and calcium cyanamide. In the first part of this study volunteers received different doses of disulfiram (125 mg and 500 + 250 mg), of calcium cyanamide (25 mg, 50 mg and 100 mg) and of ethanol (0.2 g/kg orally and 0.5 g/kg intravenously). The ensuing interactions ranged from no reaction at all to an intense hypotensive cyanamide-ethanol reaction (CER). A blood acetaldehyde concentration-effect relationship was suggested. In the second part of this study seven subjects received 50 mg of calcium cyanamide 4 hr prior to an intravenous ethanol dose of 0.2 g/kg. The maximum blood level of acetaldehyde ranged from 16 to 241 microM. Aversive interactions started to occur at acetaldehyde levels around 40-60 microM. Changes in flushing reaction and diastolic blood pressure appeared best to reflect changing blood acetaldehyde levels. As a rule, however, the expected cyanamide-ethanol and disulfiram-ethanol reactions are more clearly registered as an increase in acetaldehyde levels than as the ensuing physiological responses.

Acetaldehyde↗
PubMed1984

Acetaldehyde binds to liver cell membranes without affecting membrane function.

Acetaldehyde is a major metabolic product of ethanol and is found in high concentrations in the serum during alcohol abuse. The effects of acetaldehyde on isolated rat liver cells and on purified hepatocyte plasma membrane vesicles have been studied. In concentrations of 0-10 millimolar acetaldehyde has been shown to have no detectable effect on either hepatocyte metabolism or gross membrane function and is therefore unlikely to act as a direct metabolic poison. Acetaldehyde, however, is shown to bind to hepatocyte membranes via intermediary Schiff's base formation. The adduction of acetaldehyde to liver cell plasma membranes may have an effect on membrane structure. These findings are consistent with the hypothesis that any injurious effect of acetaldehyde on the liver may be mediated via the immune system rather than being a direct effect on cell metabolism.

Acetaldehyde↗
PubMed1988

Metabolism of acetylene and acetaldehyde by Rhodococcus rhodochrous.

We studied the ability of a soil bacterium, identified as Rhodococcus rhodochrous, to grow on acetylene and to accumulate acetaldehyde. Its maximum growth rate on acetylene was obtained at about 30 degrees C (mu = 0.11 h-1) and was independent of the concentration of this gas in air from 0.14 to 16% (v/v). During growth, acetylene was quantitatively transformed to acetaldehyde, ethanol, acetate, CO2, and biomass in proportions which varied with culture age and temperature. Growth was completely inhibited by acetaldehyde at a concentration of 10 mM. The inhibitory effect was relieved by addition of acetate. Growth on ethanol up to 140 mM did not result in acetaldehyde accumulation. Acetylene consumption was constitutive with apparent Km and Vmax equal to 250 microM and 800 nmol.min-1.(mg protein)-1, respectively. In resting cell suspensions, acetylene consumption rates decreased more rapidly under air than under nitrogen. The inhibitory effect of acetaldehyde was enhanced in the presence of oxygen. Acetaldehyde accumulation in aerobic resting cell conditions did not exceed 10 mM (440 mg/L), but under anaerobic conditions it attained more than 70 mM (3.08 g/L).

Acetaldehyde↗
PubMed1981

Acetaldehyde adducts with hemoglobin.

Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be significantly elevated in hemoglobin from alcoholics as compared with normal volunteers.

Acetaldehyde↗
PubMed1989

Acetaldehyde substoichiometrically inhibits bovine neurotubulin polymerization.

Acetaldehyde is known to form covalent adducts with tubulin and to inhibit microtubule formation. Available evidence indicates that lysine residues are prominently involved in adduct formation. Previous work has shown that lysines on tubulin can be divided into two general classes based upon their reactivity toward acetaldehyde; those of normal reactivity ("bulk" lysines) and a highly reactive lysine (HRL) located on the alpha-polypeptide subunit. We took advantage of the fact that the HRL is unreactive when tubulin is in the microtubule form to differentiate the effects of bulk from HRL adducts on tubulin polymerization. Under conditions where both bulk lysines and HRL formed adducts, 0.2 mol acetaldehyde/mol tubulin caused complete inhibition of polymerization. When we modified bulk lysines, but not HRL, tubulin polymerized essentially normally. Finally, when we first blocked bulk lysines on microtubules (HRL unreactive) using unlabeled acetaldehyde and then measured the amount of [14C]acetaldehyde adduct formed with tubulin after depolymerization (HRL reactive), 0.08 mol acetaldehyde/mol tubulin resulted in completely impaired polymerization. These data show that microtubule formation is very sensitive to even small mole fractions of acetaldehyde-modified tubulin (especially with HRL) and further suggest that small amounts of acetaldehyde adduct could be damaging to cytoskeleton function in the cell.

Acetaldehyde↗
PubMed1991

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

Acetaldehyde, the toxic product of ethanol metabolism in the liver, covalently binds to a variety of proteins. Recent studies indicate that such binding can stimulate the production of antibodies against the acetaldehyde adducts. We raised rabbit antibodies which recognized various protein-acetaldehyde conjugates but not the corresponding control proteins. Such antibodies were used in immunohistochemical studies to find out whether acetaldehyde-generated epitopes can be detected from liver specimens of 13 human subjects with different degrees of alcohol consumption. While the specimens obtained from alcohol abusers (n = 4) and alcoholics (n = 3) exhibited marked positive staining for acetaldehyde adducts inside the hepatocytes in a granular uneven pattern, the control samples (n = 6) were almost devoid of immunoreactivity. In the alcohol abusers with an early stage of alcohol-induced liver damage, staining was detected exclusively around the central veins. The data indicate that intracellular acetaldehyde adducts occur in the centrilobular region of the liver of individuals consuming excessive amounts of alcohol. Immunohistochemical detection of such adducts may prove to be of value in the early identification of alcohol abuse and in elucidating the mechanisms of alcohol-induced organ damage.

Acetaldehyde↗
PubMed1987

Potentiating effect of tyramine on acetaldehyde-induced vasoconstriction in isolated dog mesenteric arteries.

The stainless steel cannula inserting method was used to investigate the effects of acetaldehyde on isolated and perfused dog mesenteric arteries. Acetaldehyde when intraluminally administered induced a marked vasoconstriction, but repetitive injections of acetaldehyde caused tachyphylaxis. Acetaldehyde-induced vasoconstrictions were blocked by bunazosin, an alpha-1 adrenoceptor antagonist. After tyramine treatment, the acetaldehyde-induced constriction was consistently restored temporarily. It is suggested that tyramine may induce a release of norepinephrine mostly from the vesicle to the neuronal cytosol, and acetaldehyde may cause a release of norepinephrine from the cytosol to the extracellular space in the isolated canine mesenteric artery.

Acetaldehyde↗
PubMed1998

Effects of antineoplastics, antibiotics and antidiabetics on acetaldehyde metabolism after alcohol ingestion.

The main purpose of this study was to evaluate the inhibitory effects of 5-fluorouracil antineoplastics, cephem antibiotics containing the methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a 100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally. When each drug was administered singly immediately after an oral administration of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases in blood acetaldehyde concentrations. This action was also noted when ethanol was ingested 15 h after administration. The remaining drugs did not increase blood acetaldehyde concentrations. When rats were treated with carmofur at 12 h intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final treatment, blood acetaldehyde concentrations were elevated more significantly than with a single administration of carmofur. Furthermore, daily administration of cephem antibiotics containing the MTT group, latamoxef, cefamandole, cefoperazone and cefbuperazone, significantly increased blood acetaldehyde concentrations. Daily administration of sulfonylurea antidiabetics, chlorpropamide and acetohexamide, slightly increased blood acetaldehyde concentrations. Drugs causing increases in blood acetaldehyde concentrations when administration was combined with ethanol ingestion also inhibited ALDH activity in vitro. The results of the in vitro experiments roughly correlated with those of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were in the following order: carmofur >> cephem antibiotics containing the MTT group > sulfonylurea antidiabetics.

Acetaldehyde↗
PubMed1980

The effect of acetaldehyde on pancreatic and gastric secretion.

To ascertain whether any of the well-known effects of intravenous ethanol on pancreatic and gastric secretion could be due to its metabolite--acetaldehyde, a strong cytotoxic and sympathomimetic agent--acetaldehyde was given intravenously for 1 h (50, 100, and 200 mg/kg/h) in seven dogs. Acetaldehyde did not modify pancreatic secretion stimulated with secretin and caerulein, but under basal conditions 200 mg/kg/h slightly increased the volume and protein content of pancreatic juice. Acetaldehyde increased gastric secretion up to 4.03 meq/15 min in a dose-dependent manner, while serum gastrin remained unchanged. The increase of acidity persisted after propranolol and was inhibited but not abolished by ganglionic blockade. It can be concluded that physiological concentrations of acetaldehyde do not interfere with pancreatic secretion and that it is possible that the stimulatory effect of ethanol on gastric secretion is mediated at least partly through acetaldehyde.

Acetaldehyde↗
PubMed1999

Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures.

Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a consequence of both systemic and direct cellular effects. To clarify some of the pathways by which alcohol exerts its actions directly on bone cells, we investigated the formation of early osteoblast progenitors (colony-forming units for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F formation (maximal reduction +/- SEM: 50 +/- 2%; p < 0.01) at concentrations ranging from 0.04% to 0.6% that are similar to those reached in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004% and 0.02%, and completely abolished it at the dose of 0.06%. Similarly, ethanol (at concentrations > or =0.02%) and acetaldehyde (from 0.004% to 0.06%) significantly decreased the number of CFU-F in human bone marrow cultures; the mean reduction observed with ethanol was 63 +/- 12% (p < 0.05), whereas acetaldehyde completely prevented CFU-F formation at the concentration of 0.06%. These in vitro observations were confirmed by the in vivo findings that the CFU-F formation in bone marrow cultures from nine young, chronic, noncirrhotic alcoholics was significantly reduced (70 +/- 15%), compared with seven age-matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol reduced proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of the bone marrow, and this effect may contribute to the decreased bone formation observed in alcoholics.

Acetaldehyde↗
PubMed1999

Acetaldehyde prevents nuclear factor-kappa B activation and hepatic inflammation in ethanol-fed rats.

Acetaldehyde has been proposed as one of the mediators of liver injury in alcoholic liver disease. We investigated whether increased acetaldehyde levels affected the development of alcoholic liver injury. Male Wistar rats were fed a liquid diet containing fish oil and ethanol by intragastric infusion. Sustained elevations of acetaldehyde were achieved by daily treatment with two inhibitors of aldehyde dehydrogenase (ALDH): disulfiram and benzcoprine. Pathologic changes, plasma and liver acetaldehyde, nuclear factor-kappa B (NF-kappaB) and I kappa B alpha (I kappaB alpha) protein, tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase 2 (COX-2) mRNA were evaluated. Treatment with the ALDH inhibitors led to increased acetaldehyde in liver and plasma but prevented necrosis and inflammation. Steatosis was not affected. Both inhibitors decreased activation of NF-kappaB and down-regulated TNF-alpha and COX-2 expression. Decreased activation of NF-kappaB was accompanied by I kappaB alpha preservation. Acetaldehyde probably inhibits NF-kappaB activation through I kappaB alpha preservation. Down-regulation of TNF-alpha and COX-2 occur secondary to inhibition of NF-kappaB and account for the absence of necrosis and inflammation in the ALDH inhibitor-treated groups.

Acetaldehyde↗
PubMed2000

Acetaldehyde production by non-pathogenic Neisseria in human oral microflora: implications for carcinogenesis in upper aerodigestive tract.

Many epidemiological studies have identified chronic alcohol consumption as a significant risk factor for cancer of the upper aerodigestive tract (UAT) in human. Although acetaldehyde, the first metabolite from ethanol by alcohol dehydrogenase (ADH), is regarded as a carcinogen, how systemic production of acetaldehyde particularly affects the UAT remains unclear. In our study, we searched for the regional source of acetaldehyde in UAT, especially the involvement of bacteria in the human normal oral microflora. Here we demonstrate that, among the bacterial species identified from the human oral cavity, genus Neisseria had extremely high ADH activity and produced significant amounts of acetaldehyde when cultured with medium containing ethanol in vitro. The ability to produce acetaldehyde was more than 100-fold higher than that produced by any other genera we studied. Furthermore, alcohol ingestion influences the bacterial composition of the oral microflora, resulting in an increased proportion of Neisseria. Although Neisseria present in normal oral microflora is generally non-pathogenic, these findings suggest that this microbe can be a regional source of carcinogenic acetaldehyde and thus potentially play an important role in alcohol-related carcinogenesis in human UAT.

Acetaldehyde↗
PubMedDate not supplied

How to reduce 3-deoxyglucosone and acetaldehyde in peritoneal dialysis fluids.

OBJECTIVE: 3-Deoxyglucosone (3-DG) and acetaldehyde were found to be the major reactive carbonyl compounds in conventional heat-sterilized peritoneal dialysis fluids (PDFs). The aim of this study was to identify factors in the production of PDFs promoting or inhibiting the formation of acetaldehyde and 3-DG. DESIGN: Single-chamber bag PDFs with different buffer systems and pH values were analyzed for acetaldehyde. 3-Deoxyglucosone was determined in double-chamber bag PDFs with different pH values, in commercially available samples, and in double-chamber products stored under defined conditions. RESULTS: Acetaldehyde was found in the presence of lactate and malate, whereas in 2-hydroxybutanoate-buffered solution propionaldehyde was detected instead. Between pH 5.0 and 6.0 the acetaldehyde content in lactate-buffered solutions increased strongly. The concentration of 3-DG in the chamber containing glucose In double-chamber bags increased between pH 3.0 and 5.0 by a factor of 6. 3-Deoxyglucosone concentrations in commercially available products vary greatly, reflecting the different pH values of these products. A time- and temperature-dependent reaction leads to a reduction in 3-DG and an increase in 5-hydroxymethyl-furan-2-carbaldehyde during storage. CONCLUSION: Acetaldehyde is produced by a reaction that requires both lactate and glucose. Thus, its formation can be prevented by a separation of the reaction partners, glucose and lactate, in a double-chamber bag. In double-chamber bags, pH greatly influences the formation of 3-DG. Minimal formation is observed in the region of pH 3.0. This finding should be taken into account for the development of new double-chamber bag PDFs.

Acetaldehyde↗
PubMed2002

Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans.

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.

Acetaldehyde↗
PubMed1992

Influence of acetaldehyde on the vasopressor effect of serotonin in pithed rats.

In pithed rats, the intravenous (i.v.) administration of serotonin (3, 10, 30, 100, 300 and 1000 micrograms/kg) produced a dose-dependent increase in blood pressure. The pressor response to serotonin was reduced by acute acetaldehyde administration in a dose of 30 mg/kg i.v. and by 5-HT2 antagonist ketanserin (0.03 mg/kg i.v.). However, the lowest doses of acetaldehyde (10 and 20 mg/kg) were ineffective. In in vitro studies we also demonstrated that acetaldehyde (0.43 mM/l) and ketanserin (0.1 microM/l) inhibited the serotonin-induced vasoconstriction of isolated rat tail artery. In both experimental models the combination of acetaldehyde with ketanserin decreased the action of serotonin to the same extent as did ketanserin alone. In pithed rats pretreated with a high dose of ketanserin (3 mg/kg i.v.) serotonin produced hypotension by stimulation of 5-HT1 receptors. This effect was not enhanced by acetaldehyde (30 mg/kg) injection. Our data suggested that the action of acetaldehyde on the effects of serotonin in pithed rats was non-specific and independent of its interaction with serotonergic 5-HT1 and 5-HT2 receptors in blood vessels.

Acetaldehyde↗