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PubMed2002

Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells.

Acetaldehyde, the major active metabolite of alcohol, induces the activation of hepatic stellate cells (HSC), leading to over-production of alpha1(I) collagen and ultimately causing hepatic fibrosis. The underlying mechanisms of this process remain largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a potent inducer of alpha1(I) collagen production. Accumulating evidence has shown a potential role for TGF-beta1 in alcohol-induced hepatic fibrogenesis. The aims of this study were to determine the effect of acetaldehyde on TGF-beta signalling, to elucidate the underlying mechanisms as well as to evaluate its role in expression of alpha1(I) collagen gene in cultured HSC. It was hypothesized that acetaldehyde activated TGF-beta signalling by inducing the expression of elements in the TGF-beta signal transduction pathway, which might contribute to alpha1(I) collagen gene expression in cultured HSC. Initial results revealed that acetaldehyde activated TGF-beta signalling in cultured HSC. Additional studies demonstrated that acetaldehyde stimulated the secretion and activation of latent TGF-beta1, and induced the expression of the type II TGF-beta receptor (Tbeta-RII). Further experiments found cis - and trans -activating elements responsible for Tbeta-RII gene expression induced by acetaldehyde. Activation of TGF-beta signalling by acetaldehyde contributed to alpha1(I) collagen gene expression in cultured HSC. In summary, this report demonstrated that acetaldehyde stimulated TGF-beta signalling by increasing the secretion and activation of latent TGF-beta1 as well as by inducing the expression of Tbeta-RII in cultured HSC. Results from this report provided a novel insight into mechanisms by which acetaldehyde stimulated the expression of alpha1(I) collagen in HSC and a better understanding of effects of alcohol (or acetaldehyde) on hepatic fibrogenesis.

Acetaldehyde↗
PubMed1999

Effects of ethanol and its metabolite acetaldehyde on responses of the rat bladder.

OBJECTIVE: To investigate the pharmacological effects of ethanol and its metabolite acetaldehyde on isolated rat bladder muscle, and thus assess the potential influence of ethanol ingestion on the risk of urinary retention in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a pressure transducer. The acute or prolonged effects of ethanol (1-4%) or acetaldehyde (0.01, 0.1 or 1 mmol/L) were assessed on resting tension, electrical field stimulation (EFS), and bethanechol- (0.5 mmol/L), ATP- (2 mmol/L) or KCl- (127 mmol/L) induced contraction. To determine the mechanism of acetaldehyde-induced stimulation, an antihistamine, diphenhydramine was used after bethanechol stimulation. RESULTS: At the concentrations used, ethanol and acetaldehyde did not change the pH of the bathing medium. The resting tension of the muscle was not changed by ethanol, and acetaldehyde caused only a small increase in baseline tone at 1 mmol/L. Incubation with ethanol or acetaldehyde significantly suppressed contractility induced by EFS, bethanechol, ATP or KCl at each concentration (P<0.05). Contractions induced by all drugs were not changed significantly by the acute application of ethanol and the acute application of acetaldehyde did not affect contractions induced by ATP or KCl. However, EFS- or bethanechol-induced contractions were significantly enhanced (P<0. 05). The acetaldehyde-induced effects were completely blocked by the H1 antagonist, diphenhydramine (10 micromol/L). CONCLUSIONS: Ethanol did not affect resting tension but acetaldehyde and ethanol suppressed bladder muscle contractions. However, direct acetaldehyde-stimulation may release histamine and enhance contractility. This suggests that chronic alcoholism rather than acute intoxication is more likely to provoke urinary retention.

Acetaldehyde↗
PubMed2004

Effects of acetaldehyde and TNF alpha on the inhibitory kappa B-alpha protein and nuclear factor kappa B activation in hepatic stellate cells.

AIMS: Increased plasma tumour necrosis alpha (TNFalpha) and elevated monocyte nuclear factor kappa B (NF-kappaB) are associated with liver injury and inflammation in models of alcoholic liver disease and are found to be elevated in monocytes of patients with alcoholic hepatitis. Acetaldehyde enhances, whereas TNFalpha inhibits, transcription of the type I collagen promoters and type I collagen production. NF-kappaB, an inhibitor of the type I collagen promoters, is increased by both acetaldehyde and TNFalpha. This study determined the effects of acetaldehyde in comparison to the effects of TNFalpha on inhibitory kappa B-alpha (IkappaB-alpha) protein and NF-kappaB activation in hepatic stellate cells. METHODS: Activated rat hepatic stellate cells in culture were exposed to acetaldehyde or TNFalpha for short periods of time, following which the cells were harvested for the determination of IkappaB-alpha protein, IkappaB-alpha kinase activity and nuclear NF-kappaB. RESULTS: Acetaldehyde increased IkappaB-alpha kinase activity and decreased IkappaB-alpha after 10 min of exposure, with recovery towards control levels at 20 min. In contrast, TNFalpha resulted in higher IkappaB-alpha kinase activity at 20 min than at 10 min, and similar low IkappaB-alpha at 10 and 20 min. Both acetaldehyde and TNFalpha enhanced nuclear NF-kappaB (p65), but acetaldehyde alone also increased NF-kappaB (p50). CONCLUSIONS: TNFalpha and acetaldehyde independently activate NF-kappaB by rapid enhancement of IkappaB-alpha kinase activity and degradation of IkB-alpha protein. Increased TNFalpha is the principal mechanism for the elevation of NF-kappaB in severe alcoholic hepatitis. The elevation of NF-kappaB due to TNFalpha enhance liver injury, but inhibit fibrogenesis. In contrast, the effect of acetaldehyde in activating NF-kappaB is associated with increases in both liver injury and fibrogenesis, indicating that the effects of acetaldehyde on fibrogenesis are mediated by cytokines and by trans-acting factors other than NF-kappaB.

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PubMed2004

Epidermal growth factor prevents acetaldehyde-induced paracellular permeability in Caco-2 cell monolayer.

BACKGROUND: Intestinal permeability and endotoxemia play a crucial role in the pathogenesis of alcoholic liver disease. Previous studies showed that acetaldehyde disrupts intestinal epithelial barrier function and increases paracellular permeability by a tyrosine kinase-dependent mechanism. In the present study, the role of epidermal growth factor (EGF) in protection of epithelial barrier function from acetaldehyde was evaluated in Caco-2 intestinal epithelial cell monolayer. METHODS: Caco-2 cells on Transwell inserts were exposed to acetaldehyde in the absence or presence of EGF, and the paracellular permeability was evaluated by measuring transepithelial electrical resistance and unidirectional flux of inulin. Integrity of epithelial tight junctions and adherens junctions was analyzed by confocal immunofluorescence microscopy and immunoblot analysis of occludin, zonula occludens (ZO)-1, E-cadherin, and beta-catenin in the actin cytoskeleton. Reorganization of actin cytoskeletal architecture was examined by confocal microscopy. RESULTS: Acetaldehyde increased paracellular permeability to inulin and lipopolysaccharide, and EGF significantly reduced these effects of acetaldehyde in a time- and dose-dependent manner. EGF prevented acetaldehyde-induced reorganization of occludin, ZO-1, E-cadherin, and beta-catenin from the cellular junctions to the intracellular compartments. Acetaldehyde treatment induced a reorganization of actin cytoskeletal network and reduced the levels of occludin, ZO-1, E-cadherin, and beta-catenin associated with the actin cytoskeleton. EGF effectively prevented acetaldehyde-induced reorganization of actin cytoskeleton and the interaction of occludin, ZO-1, E-cadherin, and beta-catenin with the actin cytoskeleton. CONCLUSION: These results indicate that EGF attenuates acetaldehyde-induced disruption of tight junctions and adherens junctions and prevents acetaldehyde-induced reorganization of actin cytoskeleton and its interaction with occludin, ZO-1, E-cadherin, and beta-catenin.

Acetaldehyde↗
PubMed1994

Aerosolized acetaldehyde, but not ethanol, induces histamine-mediated bronchoconstriction in guinea-pigs.

It was reported that ethanol-induced bronchoconstriction was associated with elevated serum levels of acetaldehyde and histamine in Japanese asthmatic patients, but there is no study to investigate the airway response to acetaldehyde. We performed this animal study to test the hypothesis that acetaldehyde has the bronchospastic action via histamine release. First, we investigated the airway response to ascending doses (31.3, 62.5, 125, and 250 mM) of inhaled ethanol or acetaldehyde in guinea-pigs. Secondly, guinea-pigs pretreated with intraperitoneal injection of saline or 20 mg/kg diphenhydramine inhaled acetaldehyde. Finally, guinea-pigs pretreated with intraperitoneal injection of saline or 0.5 mg/kg atropine sulfate inhaled acetaldehyde. Inhalation of acetaldehyde, but not ethanol, caused bronchoconstriction in a dose-dependent manner. The bronchoconstriction induced by inhaled acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, acetaldehyde has the bronchospastic action via histamine release in guinea-pigs. It is suggested that histamine H1-antagonists may be available for preventing alcohol-induced asthma.

Acetaldehyde↗
PubMed2006

Degradation of free and sulfur-dioxide-bound acetaldehyde by malolactic lactic acid bacteria in white wine.

AIMS: Acetaldehyde is the major carbonyl compound formed during winemaking and has implications for sensory and colour qualities of wines as well as for the use of the wine preservative SO(2). The current work investigated the degradation of acetaldehyde and SO(2)-bound acetaldehyde by two commercial Oenococcus oeni starters in white wine. METHODS AND RESULTS: Wines were produced by alcoholic fermentation with commercial yeast and adjusted to pH 3.3 and 3.6. While acetaldehyde was degraded rapidly and concurrently with malic acid at both pH values, SO(2)-bound acetaldehyde caused sluggish bacterial growth. Strain differences were small. CONCLUSIONS: Efficient degradation of acetaldehyde can be achieved by commercial starters of O. oeni. According to the results, the degradation of acetaldehyde could not be separated from malolactic conversion by oenococci. While this may be desirable in white winemaking, it may be necessary to delay malolactic fermentation (MLF) in order to allow for colour development in red wines. SO(2)-bound acetaldehyde itself maybe responsible for the sluggish or stuck MLF, and thus bound SO(2) should be considered next to free SO(2) in order to evaluate malolactic fermentability. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study provides new results regarding the metabolism of acetaldehyde and SO(2)-bound acetaldehyde during the MLF in white wine. The information is of significance to the wine industry and may contribute to reducing the concentration of wine preservative SO(2).

Acetaldehyde↗
PubMed2002

Metabolic engineering of acetaldehyde production by Streptococcus thermophilus.

The process of acetaldehyde formation by the yogurt bacterium Streptococcus thermophilus is described in this paper. Attention was focused on one specific reaction for acetaldehyde formation catalyzed by serine hydroxymethyltransferase (SHMT), encoded by the glyA gene. In S. thermophilus, SHMT also possesses threonine aldolase (TA) activity, the interconversion of threonine into glycine and acetaldehyde. In this work, several wild-type S. thermophilus strains were screened for acetaldehyde production in the presence and absence of L-threonine. Supplementation of the growth medium with L-threonine led to an increase in acetaldehyde production. Furthermore, acetaldehyde formation during fermentation could be correlated to the TA activity of SHMT. To study the physiological role of SHMT, a glyA mutant was constructed by gene disruption. Inactivation of glyA resulted in a severe reduction in TA activity and complete loss of acetaldehyde formation during fermentation. Subsequently, an S. thermophilus strain was constructed in which the glyA gene was cloned under the control of a strong promoter (P(LacA)). When this strain was used for fermentation, an increase in TA activity and in acetaldehyde and folic acid production was observed. These results show that, in S. thermophilus, SHMT, displaying TA activity, constitutes the main pathway for acetaldehyde formation under our experimental conditions. These findings can be used to control and improve acetaldehyde production in fermented (dairy) products with S. thermophilus as starter culture.

Acetaldehyde↗
PubMed2002

Airway responsiveness to inhaled acetaldehyde in subjects with allergic rhinitis: relationship to methacholine responsiveness.

BACKGROUND: Asthmatic subjects have an exaggerated airway response to inhaled acetaldehyde, but no information is available on airway responsiveness to this bronchoconstrictor agent in subjects with allergic rhinitis. OBJECTIVE: The aim of this study was to determine the effect of inhaled acetaldehyde on lung function in nonasthmatic subjects with allergic rhinitis. METHODS: A total of 78 adults (43 subjects with allergic rhinitis, 16 asthmatics and 19 healthy subjects) were challenged with increased concentrations of acetaldehyde and methacholine. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV(1) (PC(20)). RESULTS: The geometric mean PC(20) acetaldehyde value for asthmatics was 35.5 mg/ml compared with 67.6 mg/ml in subjects with allergic rhinitis and with 80.0 mg/ml in healthy subjects (p < 0.001). The PC(20) acetaldehyde values in the allergic rhinitis group were also significantly lower than in the healthy control group (p = 0.04). All of the subjects with allergic rhinitis and increased responsiveness to acetaldehyde showed airway hyperresponsiveness to methacholine, but 9 patients with hyperresponsiveness to methacholine failed to respond to acetaldehyde. CONCLUSIONS: We conclude that subjects with allergic rhinitis are less responsive to inhaled acetaldehyde than asthmatic subjects, but more than healthy controls. Furthermore, only approximately half the patients with allergic rhinitis and airway hyperresponsiveness to methacholine exhibit bronchoconstriction with inhaled acetaldehyde, thus suggesting that airway hyperresponsiveness to methacholine may not be the sole factor leading to bronchoconstriction in response to acetaldehyde.

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PubMed2004

Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction.

BACKGROUND: Approximately half of the Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the present study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and to investigate the ensuing mechanisms. METHODS: Human tissue samples were prepared from the lungs resected from patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the chemical mediators released. RESULTS: Acetaldehyde (>3 x 10(-4) M) increased airway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B2 or cysteinyl-leukotrienes. A histamine (H1 receptor) antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells and degranulation of mast cells. CONCLUSIONS: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, which may be involved in bronchial smooth muscle contraction following alcohol consumption.

Acetaldehyde↗
PubMed1995

Intravenous injection of acetaldehyde but not ethanol induces histamine-mediated bronchoconstriction in guinea pigs.

Recently ethanol-induced bronchoconstriction associated with elevated serum levels of acetaldehyde and histamine was reported in Japanese asthmatic patients, but there is no investigation of the airway response to intravenous injection of acetaldehyde. We therefore performed a study in guinea pigs to test the hypothesis that intravenous injection of acetaldehyde has bronchospastic action via histamine release. At first, we investigated the airway response to increasing doses (8.0, 26.4, and 80 mg/ml) of injected ethanol or acetaldehyde in guinea pigs. Secondarily, increasing doses of acetaldehyde were injected in guinea pigs pretreated with an intraperitoneal injection of 20 mg/kg diphenhydramine or saline (control). Finally, injection of acetaldehyde was performed after intraperitoneal injection of 0.5 mg/kg atropine sulfate or saline (control). Injected acetaldehyde caused bronchoconstriction in a dose-dependent manner, but ethanol did not. The bronchoconstriction induced by injected acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, intravenous injection of acetaldehyde causes bronchoconstriction via histamine release in guinea pigs.

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PubMed1993

Acetaldehyde adducts of proteins: diagnostic and pathogenic implications in diseases caused by excessive alcohol consumption.

Alcohol abuse and alcoholism continue to be a major threat to human health. Given their increasing incidence and the detrimental impact on society, it is actually surprising that no objective, specific indicators for the early detection of alcohol-related health problems are available. A diagnostic test for a disease involving excessive alcohol consumption should be extremely specific in order to achieve positive predictive power, and: ideally it should also be very sensitive in order to identify problem drinkers in broad screening programs. The present research indicates that such a test for alcohol abuse may be provided by measurements of covalent chemical addition products (adducts) of acetaldehyde with biologically stable macromolecules. It was recently demonstrated that proteins modified with acetaldehyde are formed in vivo and can induce an antibody response as a result of alcohol consumption. Monoclonal and polyclonal antibodies raised by immunizations against acetaldehyde-modified proteins recognize acetaldehyde adducts irrespective of the nature of the carrier protein. Use of such antibodies in sensitive two-site immunoenzymatic or immunofluorometric assays has indicated that high acetaldehyde adduct concentrations exist in the erythrocytes of alcohol abusers, in healthy volunteers after a bout of drinking, and also in alcohol consuming mothers who subsequently give birth to children with foetal alcohol effects. We have developed the first immunohistochemical techniques for the detection of acetaldehyde adducts in human tissues. The centrilobular region of the liver of alcohol abusers with an early stage of histological tissue damage was found to contain acetaldehyde-modified epitopes, whereas the adducts were more widespread in advanced liver disease. The diagnostic superiority of acetaldehyde adducts as markers of ethanol consumption is due to the fact that they represent true metabolites of ethanol and allow estimations of past alcohol consumption after the ethanol has been eliminated from the body. Investigations into the formation of acetaldehyde adducts in alcohol consumers do not only have diagnostic applications but also help to explain the pathogenesis of alcohol-induced organ damage. Many types of hypersensitivity and immune responses are brought about by acetaldehyde-modified proteins. In addition, such metabolites of ethanol also aggravate liver disease through disturbed protein function and stimulation of fibrogenesis.

Acetaldehyde↗
PubMed1984

Influence of cefoperazone on ethanol and acetaldehyde metabolism in vitro.

The effect of cefoperazone on ethanol and acetaldehyde metabolism was studied in rat liver homogenates and with a purified aldehyde dehydrogenase. Rat liver homogenates were incubated with ethanol (30 mM) alone or in combination with cefoperazone (15 or 150 micrograms/g liver). Ethanol and acetaldehyde concentrations were determined at 6, 12, 18 and 24 minutes. Cefoperazone added to the incubation medium inhibited ethanol and acetaldehyde metabolism in a concentration-dependent manner. The addition of cefoperazone to rat liver homogenates incubated with acetaldehyde (300 microM), however, did not inhibit acetaldehyde disappearance for a period of 15 minutes. Purified aldehyde dehydrogenase was incubated with 300 microM acetaldehyde. When cefoperazone was added, acetaldehyde disappearance was significantly slower than without cefoperazone. The data indicate that cefoperazone inhibits ethanol metabolism in rat liver homogenates in a concentration-dependent manner. The effect of the antibiotic on acetaldehyde elimination in liver homogenate, however, depends on the concentration of acetaldehyde in the medium. The acetaldehyde dehydrogenase obtained from yeast is inhibited by cefoperazone.

Acetaldehyde↗
PubMed1999

Coagulation protein function: the influence of acetaldehyde-modified heparin on thrombin activity.

BACKGROUND: The affect of acetaldehyde-treated heparin on thrombin activity has been investigated using factor II-deficient human plasma. METHODS: It was observed that 0.021 units of heparin exerts a marked inhibition of thrombin activity (1.03 units) as measured by clotting times, prolonging the clotting times from 9.6 +/- 0.1 seconds to 24.8 +/- 0.1 seconds. However, when the heparin is preincubated with 447 mmol/L acetaldehyde at RT for 30 minutes prior to mixing with thrombin, a clotting time in excess of 200 seconds is observed. Clotting times remain elevated with heparin-acetaldehyde mixtures of 89.4, 17.9, 3.6, and 0.72 mmol/L acetaldehyde, with corresponding clotting times of > 200, 156.0 +/- 2.1, 81.6 +/- 1.0, 38.8 +/- 0.6 seconds, respectively. At 140 mumol/L acetaldehyde-heparin mixtures, the clotting time was 17.0 +/- 2.0 seconds. RESULTS: These data support the hypothesis from this laboratory that acetaldehyde-modified heparin enhances coagulation time. They further indicate that thrombin is targeted by the acetaldehyde-treated heparin. Heparin-acetaldehyde mixtures also reacted with plasma prior to the addition of thrombin to modestly prolong coagulation time. Similarly, but more effectively, thrombin/heparin mixtures increased the clotting time of acetaldehyde-exposed plasma. These data further suggest the possibility that reactions of acetaldehyde and heparin are not restricted to those with thrombin, and that they may extend to other blood factors/proteins. CONCLUSIONS: The amount of heparin (0.021 units) required to substantially affect clotting time of thrombin (1.03 units) is substantially lower than that required to prolong clotting of 0.1 mL of whole plasma (0.36 units), by an order of magnitude. It is inferred that heparin may interact with numerous cationic proteins or proteins with cationic domains in blood plasma, among them being the clotting factors.

Acetaldehyde↗
PubMed2002

Detection and localization of protein-acetaldehyde adducts in rat brain after chronic ethanol treatment.

BACKGROUND: Ethanol is metabolized to acetaldehyde in the cell, which is potentially deleterious because it can react with cellular proteins and form protein-acetaldehyde adducts, which can interfere with normal cellular function. Because the primary site of ethanol action is the brain, the present study was carried out to determine whether protein-acetaldehyde adducts are formed in rat brain after chronic ethanol administration. METHODS: Rats were treated with ethanol for 1 year, and the formation of protein-acetaldehyde adducts was examined by immunoblot analysis and localized in brain by immunohistochemical analysis by using affinity purified antibody to acetaldehyde-hemocyanin adduct. RESULTS: In the brain of rats administered ethanol for up to 1 year, protein-acetaldehyde adducts were detectable by immunoblot analysis. In brain, mitochondria was the primary site of adduct formation, unlike the liver, where the major protein-acetaldehyde adduct has been detected in the cytosol. Immunohistochemical localization of protein-acetaldehyde adducts in chronic ethanol-treated rat brain demonstrated the selective presence of adducts in cortical neurons, granule cell layer of dentate gyrus, neurons in the midbrain, and granular cell layers of cerebellum. CONCLUSIONS: These results demonstrate the significant formation of protein-acetaldehyde adducts in rat brain after ethanol ingestion. The modification of mitochondrial proteins in brain by protein-acetaldehyde adduct formation is significant because mitochondrial dysfunction has been implicated in neurodegeneration.

Acetaldehyde↗
PubMedDate not supplied

[Effect of pyruvate, threonine, and phosphoethanolamine on acetaldehyde metabolism in rats with toxic liver injury].

Pyruvate dehydrogenase, threonine aldolase and phosphoethanolamine lyase can produce acetaldehyde during normal metabolism. We studied the effect of loading with the substrates of these enzymes (pyruvate, 500 mg/kg, i.p., threonine 500 mg/kg, i.p., and phosphoethanolamine, 230 mg/kg, i.p.) on the blood concentrations of endogenous acetaldehyde and ethanol and the activities of enzymes producing and oxidizing acetaldehyde in the liver of normal rats and rats with liver injury provoked by chronic carbon tetrachloride (CCl4) treatment (0.2 ml i.p. per rat, 2 times a week during 4 weeks). Blood was collected before the treatment and then 30 min and 1 h following the administration of the substrates to intact and CCl4-treated rats. Endogenous acetaldehyde and ethanol were determined by headspace GC. The CCl4 treatment resulted in decreased liver alcohol dehydrogenase and aldehyde dehydrogenase activities and a significant elevation of liver endogenous ehtanol and a clear tendency to enhance blood acetaldehyde levels. Pyruvate increased blood endogenous acetaldehyde in CCl4-treated animals and endogenous ethanol--in the control group of animals. Threonine elevated endogenous acetaldehyde in normal rats. Phosphoethanolamine increased endogenous ethanol in the intact and CCl4 groups. At the same time, in CCl4-treated rats pyruvate administration increased the liver pyruvate dehydrogenase, threonine decreased threonine aldolase, whereas phosphoethanolamine decreased phosphoethanolamine lyase. Thus, the CCl4 effect on blood endogenous acetaldehyde and ethanol may be mediated through decreased liver ALDH and ADH activities. Liver injury promotes the accumulation of acetaldehyde, derived from physiological sources, including the degration of pyruvate and threonine by decreased acetaldehyde oxidation.

Acetaldehyde↗
PubMed2004

[Acetaldehyde concentration in acute ethanol-intoxicated patients addicted to alcohol].

Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and this is the main way of alcohol oxidizing in social drinkers. Microsomal Ethanol Oxidizing System (MEOS) is induced in ethanol addicted individuals and plays the main role in ethanol oxidation in this group. The aldehyde dehydrogenase (AIDH), enzyme oxidizing acetaldehyde to acetic acid, activity is not induced and does not get changed. This may lead to acetaldehyde cumulation in alcoholics. The aim of the study was to define the usefulness of acetaldehyde concentration measurement in the blood as the marker of alcohol addiction. 53 alcohol addicted and acutely poisoned patients (males) participated in the study. The control group was social drinkers, 43 males, accidentally poisoned with ethanol. Alcohol addiction was diagnosed according to ICD-10 criteria. Ethanol and acetaldehyde measurements were carry out on admission. The ethanol concentration in blood was measured by enzymatic method (ADH) and acetaldehyde concentration using headspace gas chromatography. Because of differences of ethanol concentrations in two examined groups (alcoholics and social drinkers) the normalization of acetaldehyde results was performed dividing acetaldehyde concentration by ethanol concentration. The results indicated higher blood acetaldehyde and ethanol concentrations in alcoholic individuals acutely poisoned with ethanol in comparison to acutely poisoned social drinkers. The acetaldehyde/ethanol ratio, used in the study, is higher in alcoholics as well and the difference is statistically significant. These results suggest the usefulness of acetaldehyde concentration measurement as a marker of ethanol addiction.

Acetaldehyde↗
PubMed1985

Clinical implications of acetaldehyde adducts with hemoglobin.

Acetaldehyde has been found to form adducts with human hemoglobin, a portion of which (15-25%) are stable to dialysis. The reaction is nonenzymatic and occurs with purified hemoglobin A. As determined by incorporation of radioactivity, the amount of stable hemoglobin adducts formed is proportional to the amount of acetaldehyde to which hemoglobin is exposed, or to the number of intermittent pulses. Reaction of hemoglobin A with 3 to 30 mM acetaldehyde significantly increases the amount of minor hemoglobins recovered following chromatography on cation exchange resin. Acetaldehyde adducts with hemoglobin involve primarily the beta chain and at least three different amino acid residues (valine, lysine and tyrosine), and two modified residues (glucosyl-valine and glucosyl-lysine). The acetaldehyde appears to be reacting with the epsilon-amino group of lysine and alpha-amino group of valine probably through an initial Schiff's base reaction. The secondary amines of glycosylated valine or glycosylated lysine residues are also proposed to be at the sites of reaction with acetaldehyde. Disubstitution of amino groups is known to occur with hexose sugar (Schwartz, Gray 1977) and by analogy, acetaldehyde might also react with the secondary amine of glycosylated residues. Acetaldehyde adduct formation with tyrosine residues may involve either a nucleophilic attack by the third or fifth carbon of the phenolic ring, analogous to formaldehyde modification of proteins (Blass, Bizzini, Raynaud 1965) or alternatively by reaction with the hydroxyl group of tyrosine. Only a portion of the stable hemoglobin-acetaldehyde adducts which were stable to 24h of dialysis could be irreversibly fixed by sodium borohydride or cyanoborohydride reduction. A greater portion however appeared to be in a non-reducible (non-carbonyl, non-amino) form. Up to 45% of the dialysis stable adducts could be reduced by sodium cyanoborohydride and be hydrolyzed to amino acid adducts if given either sufficient reduction time (2-3 weeks at 22 degrees C) or increased temperature (1-2 days at 50 degrees C). An increase in reducible adduct recovery occurred in all 5 residues detected by amino acid analysis. This suggests that the adducts that are stable to acid hydrolysis form and reverse through a reducible (e.g. Schiff base) form but that most of the time the adducts occur in a non-reducible state. At present, assay systems are not available which can detect acetaldehyde adducts in the blood of humans consuming alcohol.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaldehyde↗
PubMed1994

Acetaldehyde induces c-fos and c-jun proto-oncogenes in fat-storing cell cultures through protein kinase C activation.

Hepatic fibrosis is an important morphological feature of alcohol-induced liver injury. We previously reported that acetaldehyde stimulates collagen I and fibronectin gene transcription in rat fat-storing cell (FSC) culture. We here evaluated whether acetaldehyde increases Col I and FN gene transcription through the induction of c-fos and c-jun proto-oncogenes and studied the possible role played by protein kinase C (PKC) and c-AMP. FSCs, isolated from rat liver on a Nycodenz density gradient, were exposed to acetaldehyde for 1/2, 1, 3, 6, 12, 24 hr and for 10, 20, 30, 45, 60, 90 min in the experiments for jun and fos expression, respectively. Acetaldehyde produced a rapid and transient induction of fos mRNA (undetectable at t = 0, peak at t = 45 and still evident at t = 90). Jun mRNA was weakly expressed in unstimulated FSCs; acetaldehyde induced a prolonged activation of jun expression up to 24 hr with a peak at 3 hr. To study the role of PKC were repeated the experiments in the presence of Staurosporine and H-7. These inhibitors of PKC activity blocked the stimulatory effect of acetaldehyde on fos and jun mRNA expression. Furthermore, they abolished the stimulatory effect of acetaldehyde on collagen I and fibronectin gene expression by FSCs. Acetaldehyde increased the cell membrane PKC activity in FSC cultures in a dose-dependent way. Intracellular cAMP levels were not significantly modified by acetaldehyde in the first 30 min of incubation. We conclude that acetaldehyde increases procollagen I and fibronectin gene transcription in FSCs, possibly through c-fos and c-jun expression, and that PKC may play a regulatory role in this chain of events.

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