PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Acetaldehyde”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1990

Ethanol-inducible cytochrome P-450 activity and increase in acetaldehyde bound to microsomes after chronic administration of acetaldehyde or ethanol.

Chronic ethanol consumption results in acetaldehyde adduct formation with proteins such as haemoglobin and liver proteins in vivo. Our purpose was to study the binding of acetaldehyde to liver microsomal proteins, a site of ethanol oxidation via cytochrome P-450 (especially P-450 II E1), after chronic administration of ethanol or acetaldehyde for 21 days to rats. The liver microsomal oxidation of 1-butanol by the ethanol-inducible P-450 also was examined. Acetaldehyde bound to liver microsomal proteins was higher in ethanol-fed rats compared with acetaldehyde-treated rats (0.735 vs 0.413 nmol/mg of protein respectively). The biotransformation of n-butanol to butyraldehyde by liver microsomes was increased (by 136%) in ethanol-fed rats vs controls, whereas in acetaldehyde-treated rats this increase was much lower (only 27%). However, in this last group, a significant negative relationship between the quantity of acetaldehyde bound to microsomal proteins and the monooxygenase-catalyzed transformation of butanol by liver microsomes was demonstrated (r = -0.79, P less than 0.01). These results suggest that proteins of liver microsomes are a target for acetaldehyde binding during ethanol oxidation and such adduct formation could impair the oxidative properties of the alcohol-inducible cytochrome P-450.

Acetaldehyde↗
PubMed1990

In vivo accelerated acetaldehyde metabolism using acetaldehyde dehydrogenase-loaded erythrocytes.

Human erythrocytes were loaded with homogeneous acetaldehyde dehydrogenase (AcDH) purified from Alcaligenes Eutrophus (an enzyme species with an apparent Km for acetaldehyde similar to the mitochondrial enzyme), using an encapsulation procedure based on hypotonic haemolysis, isotonic resealing and reannealing. The AcDH-overloaded erythrocytes contained 1.55 +/- 0.25 I.U. of AcDH activity per ml of packed erythrocytes, a value 12-15 times higher than that of corresponding unloaded or native red cells. The AcDH-loaded erythrocytes were found to metabolize 4 +/- 0.8 mumol of acetaldehyde/hr/ml of red blood cells, whereas the glycolytic activity was almost unmodified. Estimates of intracellular adenine nucleotides showed 50% ATP decay in the AcDH-loaded cells when incubated in the presence of acetaldehyde concentrations higher than 50 microM, whereas the [NAD+]/[NADH] ratio was strongly decreased but to the same extent as in control cells, suggesting that this was due to the acetaldehyde itself and not to the presence of encapsulated AcDH. Similar results were obtained using mouse erythrocytes. AcDH-overloaded mouse red blood cells from donor animals were also injected intraperitoneally into compatible recipients (Balb/C) and 80 to 85% of these were found to enter into circulation within 24 hr and to circulate with a half-life of 6-7.3 days (normal half-life 11 days). Following an acute dose of ethanol (2g/kg intraperitoneally), blood levels of acetaldehyde were significantly lower in mice receiving the AcDH-loaded erythrocytes than in controls. Blood levels of ethanol were also lower in the treated mice compared to controls. These results show that AcDH-overloaded erythrocytes can perform in vitro and in vivo as bioreactors improving alcohol and acetaldehyde metabolism, and suggest that administration of these cells to alcoholic patients could be of value in restoring to normal, or improving, alcohol and acetaldehyde metabolism.

Acetaldehyde↗
PubMed1990

Cross-reactivity of antibodies raised against acetaldehyde adducts of protein with acetaldehyde adducts of phosphatidyl-ethanolamine: possible role in alcoholic cirrhosis.

This study measured the possible cross-reactivity of hapten-specific IgG antibodies purified from the sera of rabbits sensitized to an albumin-acetaldehyde conjugate [N-ethyl-rabbit serum albumin (N-ethyl-RSA)] with acetaldehyde-phosphatidylethanolamine adducts. The N-ethyl-RSA was coupled to an Affigel-10 column to affinity purify the IgG (anti-N-ethyl-RSA IgG). Dioleoyl-phosphatidylethanolamine (DOPE) was reacted with acetaldehyde to form a Schiff base, which was reduced to N-ethyl-DOPE, purified by high pressure liquid chromatography, and analyzed with direct chemical ionization mass spectrometry. Lamellar liposomes containing either 5% by weight N-ethyl-DOPE and 95% egg phosphatidylcholine or a mixture of 5% N-ethyl-DOPE, 71% DOPE, and 24% dioleoylphosphatidylcholine, as well as hexagonal phase micelles containing 5% N-ethyl-DOPE and 95% DOPE, were prepared by sonication. Anti-N-ethyl-RSA IgG was then incubated with each of these lipid mixtures for 30 min, a fluorescein-conjugated goat anti-rabbit IgG was added for an additional 30 min, and then binding of anti-N-ethyl-RSA IgG to N-ethyl-DOPE in the liposomes or micelles was measured by flow cytometry. Anti-N-ethyl-RSA IgG bound to N-ethyl-DOPE in both vesicles and hexagonal phase micelles, but the affinity was 16 times greater for the hapten in the hexagonal phase. This result demonstrates that physical presentation of the hapten can affect antibody recognition and that antibodies raised against N-ethyl-RSA can cross-react with acetaldehyde-phospholipid adducts.

Acetaldehyde↗
PubMed1991

Binding of anti-acetaldehyde IgG antibodies to hepatocytes with an acetaldehyde-phosphatidylethanolamine adduct on their surface.

We have previously shown that antibodies raised against acetaldehyde adducts of protein cross-react with an acetaldehyde adduct of dioleoylphosphatidylethanolamine, N-ethyl-dioleoylphosphatidylethanolamine, when the latter is incorporated into hexagonal phase phospholipid micelles. In the present study we demonstrate that these same IgG antibodies cross-react with N-ethyl-dioleoylphosphatidylethanolamine when this adduct is incorporated into the surface of hepatocytes. Hapten-specific IgG antibodies were purified from the sera of rabbits sensitized to an albumin-acetaldehyde conjugate that had been reduced with sodium cyanoborohydride (N-ethyl-RSA). The N-ethyl-RSA was coupled to an Affi-Gel-10 column to affinity purify the IgG. Liposomes containing N-ethyl-dioleoylphosphatidylethanolamine were fused with isolated hepatocytes, the affinity purified primary IgG antibodies were added, then fluorescein-conjugated second antibodies were added, and antibody binding to hepatocytes was measured by flow cytometry. The fluorescence of these hepatocytes was significantly greater (p less than 0.01) than control hepatocytes prepared with (1) pre-immune primary IgG antibodies with fluorescein-conjugated second antibodies, (2) no primary antibody but with fluorescein-conjugated second antibodies, and (3) no fluorescein-conjugated second antibodies.

Acetaldehyde↗
PubMed2024

Engineering a probiotic Bacillus subtilis for acetaldehyde removal: A hag locus integration to robustly express acetaldehyde dehydrogenase.

We have addressed critical challenges in probiotic design to develop a commercially viable bacterial strain capable of removing the intestinal toxin, acetaldehyde. In this study, we report the engineering of the hag locus, a σD-dependent flagellin expression site, as a stable location for robust enzyme production. We demonstrate constitutive gene expression in relevant conditions driven by the endogenous hag promoter, following a deletion of the gene encoding a post-translational regulator of σD, FlgM, and a point mutation to abrogate the binding of the translational inhibitor CsrA. Reporter constructs demonstrate activity at the hag locus after germination, with a steady increase in heterologous expression throughout outgrowth and vegetative growth. To evaluate the chassis as a spore-based probiotic solution, we identified the physiologically relevant ethanol metabolic pathway and the subsequent accumulation of gut-derived acetaldehyde following alcohol consumption. We integrated a Cupriavidus necator aldehyde dehydrogenase gene (acoD) into the hag locus under the control of the flagellin promoter and observed a rapid reduction in acetaldehyde levels in gut-simulated conditions post-germination. This work demonstrates a promising approach for the development of genetically engineered spore-based probiotics.

Acetaldehyde↗
PubMed1991

Atherosclerosis and acetaldehyde metabolism in blood.

Acetaldehyde elimination in blood homogenates and erythrocyte aldehyde dehydrogenase (ALDH) activity were studied in 64 patients operated before the age of 60 years because of symptomatic stenosis of aorta, iliac, or carotid arteries and in 38 healthy controls. The disappearance of acetaldehyde in blood homogenates was biphasic. Patients showed an enhanced elimination of acetaldehyde during the second phase (30-60 min), as compared to controls (T1/2 of acetaldehyde was 103 +/- 47 and 198 +/- 93 min, respectively, P less than 0.001). No correlation was found between ALDH activity and acetaldehyde elimination rate. Acetaldehyde elimination in blood homogenates and [14C]acetaldehyde binding to plasma proteins, hemoglobin, and erythrocyte membranes were studied in 10 patients with atherosclerotic disease and in 12 healthy controls. There was a significant correlation between unstable binding of [14C]acetaldehyde to plasma proteins and the half-life of acetaldehyde in the elimination test (p = 0.74, P less than 0.005). Fractionation of plasma proteins after incubation with [14C]acetaldehyde revealed no difference between patients and controls in the distribution of radioactivity. The binding of [14C]acetaldehyde to hemoglobin or erythrocyte membranes did not differ between patients and controls. These results indicate that patients with angiopathy and an enhanced acetaldehyde elimination in blood have reduced binding of acetaldehyde to plasma proteins. As unstable binding of acetaldehyde to proteins is known to involve free amino groups of amino acid residues, modification of these residues in atherosclerotic disease is conceivable.

Acetaldehyde↗
PubMedDate not supplied

Breath acetaldehyde following ethanol consumption.

Five pairs of volunteers were studied to determine the effect of drinking ethanol on breath acetaldehyde levels. On a given study day, samples of breath were obtained for measurement of acetaldehyde and ethanol from both participants at t = -1 h, t = -0.5 h, and at t = 0 to obtain baseline values. The drinkers were then given ethanol (0.3 g/kg body weight), and the controls given an equal volume of tap water. Breath samples were then taken at 0.5, 1, 1.5, 2 h, and hourly until t = 6 h. The last sample taken was at t = 23.5 h. Acetaldehyde levels in breath were quantified with a fluorigenic high-performance liquid chromatographic assay. Blood ethanol was approximated using a breath analyzer. Acetaldehyde in breath rose 50-fold at the 0.5-h, time point and returned to levels not significantly different from baseline values by 3-4 h. The mean peak blood ethanol values reached 0.055%. The t 1/2 elimination for ethanol was 1.6 h, and that for acetaldehyde was 2.25 h. Elimination of both acetaldehyde and ethanol in breath were initially 0 order. A significant correlation (r = 0.74) was found between baseline breath acetaldehyde levels and peak acetaldehyde levels. We conclude that acetaldehyde resulting from ethanol intake rapidly partitions into breath. The correlation of baseline breath acetaldehyde values with peak values found after an ethanol challenge indicate that measurement of breath acetaldehyde may be useful in the identification of individual differences in ethanol metabolism.

Acetaldehyde↗
PubMedDate not supplied

The formation of stable acetaldehyde-hemoglobin adducts in a red blood cell model.

The formation of stable hemoglobin adducts was examined (in the absence of an added reducing agent) in metabolizing red blood cells (RBCs) exposed to micromolar concentrations of acetaldehyde for up to 48 hours in vitro. The rapid disappearance of acetaldehyde due to oxidation by RBC aldehyde dehydrogenase was prevented by pretreating the cells with the inhibitor cyanamide. The RBCs remained viable for 48 hours (37 degrees C) as determined by cell hemolysis and glycolytic activity. [14C]acetaldehyde-modified hemoglobin was assessed in untreated and in cyanamide-pretreated cells. In untreated cells, after 3 hours of exposure to 50 and 200 nmol/ml of [14C]acetaldehyde, the molar ratios of acetaldehyde to hemoglobin were 0.00069 and 0.0038, respectively; [14C]acetaldehyde concentrations decreased to less than 4% of the initial levels within 3 hours. In cyanamide-pretreated RBCs, the molar ratios of acetaldehyde bound to hemoglobin ranged from 0.0013 after 3 hours of exposure to 20 nmol/ml [14C]acetaldehyde up to 0.039 after 48 hours of exposure to 200 nmol/ml [14C]acetaldehyde. Following tryptic digestion of [14C]acetaldehyde-hemoglobin and separation of peptides by high-performance liquid chromatography, significant incorporation of [14C]acetaldehyde was observed in nine peptides. Modifications of the labeled peptides remain to be characterized.

Acetaldehyde↗
PubMed1991

Acetaldehyde-mediated cilia dysfunction in bovine bronchial epithelial cells.

Acetaldehyde, which is present in significant concentrations in cigarette smoke and is elevated during alcohol ingestion, has been demonstrated to impair mucociliary clearance of the lung. Acetaldehyde is also known to impair protein function through the formation of acetaldehyde-protein adducts. We hypothesized that acetaldehyde impairs bronchial epithelial cilia motion by inhibiting cilia dynein adenosinetriphosphatase (ATPase) activity through the formation of acetaldehyde adducts with cilia proteins. Acetaldehyde induced concentration- and time-dependent slowing of cilia beating and cilia-derived dynein ATPase activity in primary cultures and isolated axonemes of bovine airway epithelial cells. Cilia slowing and ATPase inhibitory effects were also observed with related aldehydes but not with ethanol. Acetaldehyde binding, assessed by gel electrophoresis using [14C] acetaldehyde, was demonstrated to occur with the dynein heavy chains and with tubulin and closely paralleled ATPase inhibition. We conclude that acetaldehyde directly impairs bronchial cilia function causing slowing of cilia beating, inhibits cilia dynein ATPase activity, and binds to cilia proteins critical for motion including dynein and tubulin. These data suggest that acetaldehyde-induced cilia dysfunction may be related to direct cilia ATPase inactivation and adduct formation with cilia dynein and tubulin. This may be an important mechanism by which airway host defenses are impaired in clinical settings where acetaldehyde exposure occurs, e.g., with cigarette smoking and alcohol ingestion.

Acetaldehyde↗
PubMed1978

The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism.

Previous studies in vivo and with isolated perfused rat livers have suggested that the deleterious effect of ethanol on hepatic pyridoxal 5'-phosphate metabolism is mediated by acetaldehyde. Inasmuch as acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it has also been postulated that acetaldehyde accelerates pyridoxal phosphate degradation by displacing this coenzyme from binding proteins, which protect it against hydrolysis. To test these hypotheses, studies have been performed with isolated rat hepatocytes, subcellular fractions of rat liver, and human erythrocytes. Ethanol oxidation lowered the pyridoxal phosphate content of isolated liver cells when acetaldehyde oxidation was inhibited by either disulfiram or prior treatment of rats with cyanamide. Additions of 7.5 mM acetaldehyde alone at 40-min intervals to cell suspensions decreased hepatic pyridoxal phosphate content only slightly because acetaldehyde was rapidly metabolized. However, when acetaldehyde oxidation and reduction were inhibited by cyanamide treatment and by 4-methyl-pyrazole and isobutyramide, respectively, a 40% decrease in hepatic pyridoxal phosphate content was observed in 80 min of incubation. In equilibrium dialysis experiments, acetaldehyde, 7.5 and 15 mM, displaced protein-bound pyridoxal phosphate in undialyzed hepatic cytosol and in hemolysate supernate containing added pyridoxal phosphate. In the presence of alkaline phosphatase, acetaldehyde accelerated the degradation of pyridoxal phosphate in dialyzed hemolysate supernate and hepatic cytosol with added pyridoxal phosphate. Acetaldehyde also inhibits tyrosine aminotransferase. The kinetics of inhibition were mixed competitive-noncompetitive with respect to pyridoxal phosphate. These observations support the hypothesis that the deleterious effect of ethanol oxidation on pyridoxal phosphate metabolism is mediated at least in part by acetaldehyde which displaces this coenzyme from protein binding, thereby enhancing its degradation.

Acetaldehyde↗
PubMed1976

Characteristics of acetaldehyde oxidation in rat liver mitochondria.

Rat liver mitochondria oxidized acetaldehyde (180 muM) at the rate of approximately 12 nmol/min/mg of protein at 37 degrees. This was stimulated by 88% with the addition of ADP. The ADP/O ratio (2.6) was similar to that with glutamate as substrate. 2,4-Dinitrophenol and phenazine methosulfate also stimulated the rate of acetaldehyde oxidation in the mitochondria. By contrast, acetaldehyde metabolism was virtually abolished by rotenone and antimycin A. These results indicate that acetaldehyde oxidation is linked to the mitochondrial respiratory chain and coupled with mitochondrial oxidative phosphorylation. Indeed, little acetaldehyde was metabolized when mitochondrial membranes were disrupted by sodium deoxycholate. In the disrupted mitochondria, however, acetaldehyde oxidation was fully recovered by addition of NAD+, suggesting that the ability of mitochondria to supply NAD+ controls the rate of acetaldehyde oxidation in intact mitochondria. The stimulatory effect of ADP on mitochondrial acetaldehyde oxidation was diminished by increasing the acetaldehyde concentration. Concomitantly, the ADP/O ratio decreased, suggesting an inhibitory effect of high concentrations of acetaldehyde on mitochondrial respiration. Chronic feeding of ethanol significantly reduced the capacity of intact liver mitochondria to oxidize acetaldehyde. This was associated with a significant reduction of the mitochondrial respiration. By contrast, the activity of aldehyde dehydrogenase in disrupted mitochondria remained unchanged.

Acetaldehyde↗
PubMed1991

Ethanol-induced CTA mediated by acetaldehyde through central catecholamine activity.

The possible involvement of catecholamines (CA) in the mediation of acetaldehyde's conditioned taste aversion (CTA) was examined by testing the effects of alpha-methyl-para-tyrosine (AMPT, a tyrosine hydroxylase inhibitor) on the CTAs produced by acetaldehyde. AMPT blocked the acquisition of the CTA normally produced by a low dose of acetaldehyde (0.2 g/kg), but had no significant effect on CTA produced by a high dose of acetaldehyde (0.3 g/kg). In a second study, acetaldehyde's role in the CTA produced by ethanol was investigated using the pre-exposure conditioned taste aversion paradigm. Pre-exposure to acetaldehyde (both doses) blocked the ethanol CTAs but when pre-exposure with acetaldehyde was coupled with AMPT, only the larger dose of acetaldehyde blocked the ethanol aversion. These results suggest that while the CTA to the low dose of acetaldehyde may be primarily central and catecholamine-mediated, the mechanism underlying the high dose CTA is probably peripheral and emetic in nature. These findings support the conclusion that acetaldehyde may be mediating many of the actions of ethanol.

Acetaldehyde↗