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At least 19 recordsLinked to original sources

PubMed1983

Elimination of artifactual acetaldehyde in the measurement of human blood acetaldehyde by the use of polyethylene glycol and sodium azide: normal blood acetaldehyde levels in the dog and human after ethanol.

A new procedure is described for the preparation of human blood samples for analysis of acetaldehyde and ethanol by head space gas chromatography. High concentrations of polyethylene glycol were used to remove the hemoglobin and approximately 50% of the plasma protein. Artifactual formation of acetaldehyde from ethanol was inhibited by sodium azide. Using this method, no artifactual acetaldehyde was detectable in human, dog, sheep, and rat blood when spiked with ethanol in final concentrations of 65 mM. The recovery of added acetaldehyde was approximately 80% for human dog, and sheep blood, whereas it was only 30% for rat blood. Following ethanol administration, acetaldehyde levels were determined in blood taken from the pulmonary artery and descending aorta of the dog and human, and also from the hepatic vein of the latter. The relative blood acetaldehyde concentrations at these sites were hepatic vein greater than pulmonary artery greater than descending aorta.

Acetaldehyde↗

PubMed2000

Covalent adducts of proteins with acetaldehyde in the liver as a result of acetaldehyde administration in drinking water.

BACKGROUND/AIMS: Acetaldehyde, the first metabolic product of ethanol, has been suggested to be responsible for several adverse effects of ethanol through its ability to form covalent adducts with proteins and cellular constituents. It has recently been suggested that acetaldehyde derived from microbial ethanol oxidation in the gut could also contribute to the effects of ethanol in the liver. The present work aimed to examine whether modification of proteins by acetaldehyde occurs in rat liver as a result of acetaldehyde administration in drinking water. METHODS: Rats were fed with either 0.7% acetaldehyde (n=10) or water (n=10) for 11 weeks. At the end of the feeding period, liver specimens were processed for immunohistochemistry for protein adducts with acetaldehyde and for hepatic cell type-specific protein markers. RESULTS: Mild fatty change was found in the liver of the acetaldehyde-treated animals but not in the control animals. Immunohistochemical stainings for acetaldehyde adducts revealed intensive positive staining for acetaldehyde adducts in eight (80%) of the animals fed with acetaldehyde. The adducts were predominantly perivenular, although positive staining also occurred along the sinusoids and in the periportal area. Double immunofluorescence staining experiments revealed that hepatocytes were the primary targets of acetaldehyde adduct deposition, although stellate cells and Kupffer cells also showed weak positive reactions. CONCLUSIONS: The present data indicate that acetaldehyde-protein adducts are formed in the liver of animals following acetaldehyde administration in drinking water, which may contribute to the hepatotoxicity of extrahepatic acetaldehyde. These findings should be implicated in studies on the extrahepatic pathways of ethanol oxidation.

Acetaldehyde↗

PubMed2005

Aldehyde dehydrogenase 2 activity affects symptoms produced by an intraperitoneal acetaldehyde injection, but not acetaldehyde lethality.

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals are inactive ALDH2 phenotype; acute acetaldehyde toxicity has not been evaluated in these populations. We compared the acute acetaldehyde toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice who were administered an intraperitoneal (ip) injection of a single dose of acetaldehyde. This comparison was made based on the LD(50) values of acetaldehyde and the symptoms following the ip injection. Blood acetaldehyde level was measured in the 400 mg/kg dose group. Immediately after administration of acetaldehyde, the mice exhibited hypoactivity and staggering gait. Subsequently, symptoms such as pale skin, prone position, coma, and abnormal deep respiration were observed. In cases of death, dyspnea, wheezing, and hypothermia were observed from 15 to 30 min after the administration. In cases of survival, crouching, bradypnea, flushing and piloerection were observed. Significant latency of symptom recovery was found in the Aldh2+/- mice as compared with the Aldh2+/+ mice; however, no statistical difference was observed in the acetaldehyde LD(50) values. This might be attributable to the absence of a significant difference in the blood acetaldehyde concentrations in both mice during the first 0-15 min following administration; however, acetaldehyde elimination delay was observed in the Aldh2-/- mice as compared with the Aldh2+/+ mice. Acetaldehyde toxicity difference was observed between the Aldh2+/+ and Aldh2-/- mice; however, no difference in acetaldehyde lethality was observed by administration of a single dose of an ip acetaldehyde injection.

Acetaldehyde↗

PubMed1983

Acetaldehyde adducts with proteins: binding of [14C]acetaldehyde to serum albumin.

Acetaldehyde, the immediate oxidation product of ethanol metabolism, was assessed for its ability to bind covalently to a purified protein in solution. Bovine serum albumin (BSA) was used as the model protein incubated in the presence of 0.2 mM [14C]acetaldehyde at pH 7.4 and at 37 degrees C. Acetaldehyde formed both stable and unstable adducts with serum albumin. Unstable adducts were identified following stabilization with the reducing agent sodium borohydride. We examined both types of binding using trichloroacetic acid precipitation, gel filtration, and dialysis as means to separate bound from free acetaldehyde. All three methods of analysis gave comparable results except that the number of stable acetaldehyde adducts with albumin were significantly lower following separation by dialysis. The effects of L-cysteine, L-lysine, and reduced glutathione were assessed for their abilities as competitive reagents to decrease binding of [14C]acetaldehyde to BSA. Addition of cysteine caused a rather dramatic concentration-dependent reduction in [14C]acetaldehyde binding to BSA when compared to that caused by lysine which displayed a relatively mild effect on covalent binding. The presence of glutathione caused a concentration-dependent decrease in protein-bound radioactivity that was stronger than that by lysine but not as effective as cysteine. The ability of each reagent to reverse the formation of preformed acetaldehyde adducts with BSA was also examined. Only L-cysteine effectively decreased the number of unstable acetaldehyde adducts with BSA while stable binding of acetaldehyde remained essentially unaffected by any of the three reagents. These results indicate that acetaldehyde can covalently bind to protein and form unstable as well as stable adducts.

Acetaldehyde↗

PubMed1986

Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts.

Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 microM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.

Acetaldehyde↗

PubMed1995

Validated fluorimetric HPLC analysis of acetaldehyde in hemoglobin fractions separated by cation exchange chromatography: three new peaks associated with acetaldehyde.

Stable hemoglobin-acetaldehyde adducts present in hemoglobin fractions separated by polyaspartic acid cation exchange chromatography were quantified by fluorimetric HPLC. The fluorescent species eluted from the HPLC was confirmed by mass spectrometry to be consistent with the expected product from reaction of acetaldehyde, 1,3-cyclohexanedione (CHD), and ammonium ion. Hemolysate (2.2 mM hemoglobin) was incubated in equivalent volumes of either phosphate-buffered saline or 5 mM acetaldehyde at 37 degrees C for 30 min and washed three times with H2O to remove free acetaldehyde and labile adducts before the injection of 14.7 mg hemoglobin onto the cation exchange column. Fluorimetric HPLC analysis of hemolysate samples either with or without in vitro reaction with acetaldehyde revealed that most acetaldehyde resides in the hemoglobin A0 fraction. The reaction with acetaldehyde in vitro resulted in a significant increase in fast-eluting minor hemoglobin species on cation exchange chromatography concomitant with increased acetaldehyde in the HbA1a+b, HbA1c, and HbA1-AcH fractions. We report three new cation exchange chromatographic peaks after reaction with acetaldehyde: HbA1-AcH-3, HbA1c-1, and HbA0-1. Each new peak was found to associate with a significant quantity of CHD-reactive acetaldehyde. These experiments provide additional evidence that stable adducts form between acetaldehyde and hemoglobin and that these adducts occur in multiple hemoglobin species separated by cation exchange chromatography. Further characterization and structural assignment of these species are warranted in view of their potential utility as markers for ethanol intake.

Acetaldehyde↗

PubMed2000

High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde.

BACKGROUND: Due to a point mutation, aldehyde dehydrogenase-2 (ALDH2) isoenzyme is deficient in 30% to 50% of Asians. Among Asian ALDH2-deficient heavy drinkers, the risk for digestive tract cancers is markedly increased (odds ratio 3.4-54.2). The reason for this is unknown but could be due to the local carcinogenic action of acetaldehyde. METHODS: Salivary and blood acetaldehyde levels were determined in 20 healthy Asians after a moderate dose of alcohol (0.5 g/kg of body weight). Salivary acetaldehyde production capacity from ethanol in vitro was measured also. ALDH2 genotype of the Asians was determined from isolated leukocyte-deoxyribonucleic acid by polymerase chain reaction/restriction fragment length polymorphism method. Acetaldehyde content of parotid gland saliva was measured in three ALDH2-deficient Asians and three White subjects with normal ALDH2 after the same dose of ethanol. RESULTS: Seven of the Asians were heterozygous for the mutant ALDH2*2 allele (flushers). They had two to three times higher salivary acetaldehyde levels than the Asians (n = 13) with normal ALDH2 throughout the follow-up period of 240 min (p < 0.001). Only in the flushers did the parotid gland contribute to salivary acetaldehyde production. The in vitro capacity of saliva to produce acetaldehyde from ethanol was equal in both groups. The flushers' blood acetaldehyde levels were only one ninth of the levels in saliva. CONCLUSIONS: By using this human "knockout model" for deficient acetaldehyde removal, we found that in addition to oral microflora, acetaldehyde in saliva may also originate from the oxidation of ethanol in the parotid gland. When combined with earlier epidemiological data, these results offer a strong evidence for the local carcinogenic action of acetaldehyde in humans.

Acetaldehyde↗

PubMed1985

Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo.

In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.

Acetaldehyde↗

PubMed1981

The effect of cyanamide on acetaldehyde oxidation by isolated rat liver mitochondria and on the inhibition of pyruvate oxidation by acetaldehyde.

Compared to other substrates, the oxidation of pyruvate by isolated mitochondria is especially sensitive to inhibition by acetaldehyde. It is not known whether this inhibition represents a direct effect of acetaldehyde or requires the metabolism of acetaldehyde. Experiments were therefore carried out in the presence of cyanamide, an inhibitor of aldehyde dehydrogenase. After a brief incubation period, cyanamide inhibited the state 4 and state 3 rate of acetaldehyde (0.1-1.0 mM) oxidation by isolated rat liver mitochondria. Little inhibition was found in the absence of the incubation period. Maximum inhibition was found at cyanamide concentrations of 0.01 to 0.033 mM. Cyanamide also inhibited the activity of aldehyde dehydrogenase assayed in disrupted mitochondrial fractions. The inhibition by cyanamide was specific since cyanamide did not affect mitochondrial oxidation of succinate, glutamate, or pyruvate. Acetaldehyde inhibited the state 3 rate of pyruvate oxidation by liver mitochondria. Despite preventing acetaldehyde oxidation, cyanamide did not prevent the inhibition of pyruvate oxidation by acetaldehyde. These results indicate that (a) cyanamide can be used as an effective in vitro inhibitor of acetaldehyde oxidation and (b) the unique sensitivity of pyruvate oxidation to acetaldehyde represents a direct effect of acetaldehyde on pyruvate dehydrogenase.

Acetaldehyde↗

PubMed1996

Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin complexes after the consumption of red and white wine: in vitro effects of flavonoids, vitamin E, and other dietary antioxidants on cytotoxic complexes.

After the consumption of ethanol, acetaldehyde levels increase in the serum, and the serum develops a nondialyzable cytotoxic activity caused by the formation of unstable acetaldehyde-albumin complexes. The concentration of acetaldehyde in the serum and the cytotoxic activity in serum albumin 8.5 hr after six healthy volunteers began to drink 94 g of ethanol were significantly less when the ethanol was consumed as red wine than as white wine. The serum acetaldehyde was measured by a fluorigenic HPLC assay, and the cytotoxic activity in albumin was determined using two different assays based on dissimilar endpoints: (1) detachment of adherent A9 cells and (2) impairment of the ability of A9 cells to reduce tetrazolium. When serum obtained from five other healthy volunteers after the consumption of white wine was incubated at 37 degrees C for 3 hr with a number of dietary antioxidants at a concentration of 100 mumol/liter, the cytotoxicity of the albumin was markedly reduced. The antioxidants studied consisted of six flavonoids (kaempherol, fisetin, quercetin catechin, taxifolin, and coumarin) and three nonflavonoids (salicylic acid, tannic acid, and alpha-tocopherol). In the cases of alpha-tocopherol, a statistically significant reduction of cytotoxicity was observed at a concentration of 10 mumol/liter. In addition, the cytotoxicity of artificially prepared acetaldehyde-albumin complexes was significantly reduced when such complexes were incubated with 50 to 100 mumol/liter of kaempherol, fisetin, quercetin, coumarin or salicylic acid, or 10 mumol/liter of alpha-tocopherol at 37 degrees C for 3 hr. Evidently, in vitro, flavonoid and nonflavonoid dietary constituents reduce the amount of unstable acetaldehyde-albumin complexes found in both postalcohol serum and in artificially produced acetaldehyde-albumin complexes. The difference in the amount of unstable acetaldehyde-albumin complexes found in serum after the consumption of red and white wine may therefore be caused by the higher concentration of antioxidants, including flavonoids, in red wine than in white wine. Because acetaldehyde and acetaldehyde-albumin complexes have been implicated in the pathogenesis of alcohol-mediated tissue damage, these data suggest that dietary antioxidants may influence the biological consequences of excess alcohol consumption.

Acetaldehyde↗

PubMed2003

Binding of acetaldehyde to a glutathione metabolite: mass spectrometric characterization of an acetaldehyde-cysteinylglycine conjugate.

BACKGROUND: Ethanol administration decreases hepatic glutathione levels and increases urinary sulfhydryl excretion. Ethanol-induced liver injury is blunted by the administration of glutathione precursors. Acetaldehyde generated in the metabolism of ethanol binds to a number of amino acid residues in proteins and peptides, but it does not react readily with glutathione. Due to the possible role of acetaldehyde in cysteine and glutathione homeostasis, we investigated the reaction of acetaldehyde to cysteinylglycine, the dipeptide generated in vivo in the hydrolysis of glutathione by gamma-glutamyltransferase. METHODS: A conjugate between acetaldehyde and cysteinylglycine was generated under physiologically relevant conditions, both in vitro and in vivo. It was separated by a new reverse-phase high-performance liquid chromatography method and identified by electrospray ionization/ion trap tandem mass spectrometric analysis. RESULTS: The conjugate with a stoichiometry of 1:1 between cysteinylglycine and acetaldehyde is most rapidly generated in vitro and was identified by mass spectroscopy as 2-methyl-thiazolidine-4-carbonyl-glycine. This thiazolidine derivative is stable in vitro and in biological fluids of rats. The conjugate was present in high concentrations in the bile of rats pretreated with ethanol and an inhibitor of aldehyde dehydrogenase. CONCLUSIONS: The sequestering of cysteinylglycine by acetaldehyde occurs rapidly under physiologic conditions. Long-lived sulfur-containing biomolecules that incorporate acetaldehyde might affect cysteine and glutathione homeostasis and may also play a protective role by reducing circulating acetaldehyde levels. The acetaldehyde conjugate or its metabolic products could potentially serve as markers of ethanol consumption.

Acetaldehyde↗

PubMedDate not supplied

Accumulation of acetaldehyde in alcohol-sensitive Japanese: relation to ethanol and acetaldehyde oxidizing capacity.

The metabolism of ethanol and its oxidation product, acetaldehyde, was studied in Japanese volunteers. Subjects who responded by facial flushing and tachycardia were found to accumulate acetaldehyde during ethanol intoxication, in contrast to the near absence of blood acetaldehyde in nonflushing subjects. There were large individual variations in acetaldehyde accumulation observed in the former group, and this accumulation correlated well with the intensity of the physiological responses, but not with rate of ethanol elimination. Oral pretreatment with the alcohol dehydrogenase inhibitor, 4-methylpyrazole, reduced ethanol elimination by 15-25% and strongly suppressed acetaldehyde accumulation. However, here too there was no relation between individual ethanol elimination rate and acetaldehyde accumulation. Furthermore, the change in the blood lactate/pyruvate concentration ratio after ethanol intake was apparently unrelated to the degree of acetaldehyde accumulation. These results, combined with our previous observation of a strong negative correlation between increase in heart rate and activity of cytosolic aldehyde dehydrogenase in erythrocytes, suggest that in flushing Orientals lacking the low-Km aldehyde dehydrogenase isozyme, the alternative cytosolic enzyme is responsible for acetaldehyde oxidation, and its activity probably determines the individual variation of acetaldehyde-mediated physiological responses.

Acetaldehyde↗

PubMedDate not supplied

Improved method for acetaldehyde in plasma and hemoglobin-associated acetaldehyde: results in teetotalers and alcoholics reporting for treatment.

A fluorigenic high performance liquid chromatographic (HPLC) assay for the determination of acetaldehyde in plasma and hemoglobin-associated acetaldehyde is described. The assay is based on the reaction of acetaldehyde with two molecules of 1,3-cyclohexanedione in the presence of ammonium ion to form a fluorescent species followed by reverse phase HPLC separation of specific aldehyde derived compounds. The assay is specific; and has sensitivity in the picomole range, with intraassay precision of less that 3.5% and interassay precision of less than 15%. The total run time is less than 6 minutes on HPLC. Hemoglobin-associated acetaldehyde levels were higher than the levels found in plasma. Endogenous levels of acetaldehyde in samples obtained from teetotalers were found to be 0.43 +/- 0.04 (S.D.) microM in plasma and 74.2 +/- 16.1 nmol/g protein as hemoglobin-associated acetaldehyde. The levels of both plasma acetaldehyde and hemoglobin-associated acetaldehyde were significantly higher in patients reporting to a center for alcohol treatment than the levels encountered in teetotalers.

Acetaldehyde↗

PubMed2002

Generation of protein adducts with malondialdehyde and acetaldehyde in muscles with predominantly type I or type II fibers in rats exposed to ethanol and the acetaldehyde dehydrogenase inhibitor cyanamide.

BACKGROUND: Alcoholic myopathy is known to primarily affect type II muscle fibers (glycolytic, fast-twitch, anaerobic), whereas type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. OBJECTIVE: We investigated whether aldehyde-derived adducts of proteins with malondialdehyde and acetaldehyde are formed in muscle of rats as a result of acute exposure to ethanol and acetaldehyde. The differences between type I muscle, type II muscle, and liver tissue were also assessed. DESIGN: The formation and distribution of malondialdehyde- and acetaldehyde-protein adducts were studied with immunohistochemistry in soleus (type I) muscle, plantaris (type II) muscle, and liver in 4 groups of rats. The different groups were administered saline (control), cyanamide (an acetaldehyde dehydrogenase inhibitor), ethanol, and cyanamide + ethanol. RESULTS: Treatment of rats with ethanol and cyanamide + ethanol increased the amount of aldehyde-derived protein adducts in both soleus and plantaris muscle. The greatest responses in malondialdehyde-protein and acetaldehyde-protein adducts were observed in plantaris muscle, in which the effect of alcohol was further potentiated by cyanamide pretreatment. Malondialdehyde- and acetaldehyde-protein adducts were also found in liver specimens from rats treated with ethanol and ethanol + cyanamide; the most abundant amounts were found in rats given cyanamide pretreatment. CONCLUSIONS: Acute ethanol administration increases protein adducts with malondialdehyde and acetaldehyde, primarily in type II muscle. This may be associated with the increased susceptibility of anaerobic muscle to alcohol toxicity. Higher acetaldehyde concentrations exacerbate adduct formation, especially in type II-predominant muscles. The present findings are relevant to studies on the pathogenesis of alcohol-induced myopathy.

Acetaldehyde↗

PubMed1984

The effect of acetaldehyde concentrations on the relative rates of formation of acetaldehyde-modified hemoglobins.

The effect of various concentrations of acetaldehyde (0, 0.05, 0.1, 0.25, 0.5, 1.0, and 5.0 mM) on the relative rates of formation of hemoglobin acetaldehyde adducts detected in fractions eluted from cation exchange high-pressure liquid chromatography (HPLC) was investigated. When the hemoglobin and acetaldehyde mixtures were incubated at 37 degrees C for various time intervals up to 24 hr, increased amounts of HbA1c could be observed after 2 hr incubation with 1 mM or greater concentrations of acetaldehyde, or after 4 hr incubation with at least 0.5 mM acetaldehyde. An increase in the HbA1a + b fraction was not observed with 4 hr incubation time until the acetaldehyde level reached 1 mM. The HPLC method detected no difference in minor hemoglobins from alcoholic and normal subjects. Incubation of red blood cells at 37 degrees C for 1 hr with six consecutive pulses of 0.05 mM [14C]acetaldehyde showed no differences in the amounts of minor hemoglobins determined chromatographically at various pulse intervals. However, the measure of the 14C-label incorporation into hemoglobin showed that adducts eluting in the HbA1a+b fraction were formed at a faster rate than those eluting in the HbA1c or HbA0 fraction, respectively. The specific activities of the HbA1a+b fractions at 2, 4, and 6 pulses were 34, 128, and 949 cpm/mg hemoglobin; those of the HbA1c fraction were 15, 58, and 174 cpm/mg hemoglobin. This evidence of modification of hemoglobin by physiological levels of acetaldehyde from 14C-label incorporation suggests that an assay more sensitive than chromatographic separation of adducts might be clinically useful in detecting alcoholism or monitoring alcohol detoxification programs.

Acetaldehyde↗

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↗

PubMed1995

Antibodies made against a formaldehyde-protein adduct cross react with an acetaldehyde-protein adduct. Implications for the origin of antibodies in human serum which recognize acetaldehyde-protein adducts.

Acetaldehyde, the major metabolite of ethanol, reacts with lysine and other free amino groups on proteins to form acetaldehyde-protein adducts. The presence of antibodies which recognize such acetaldehyde-protein adducts in sera from alcoholics has been attributed to an immune response to such adducts. Complicating this conclusion is the finding that sera from non-alcoholic control subjects also contain antibodies which recognize acetaldehyde-protein adducts. In the current research we sought to determine whether antibodies which recognize epitopes formed by the reaction of a protein with acetaldehyde can be formed in response to a protein modified with a structurally related protein adduct. We modified lysine residues on apolipoprotein (apo) B-100 with acetaldehyde and formaldehyde under reducing conditions, to form epsilon-N-methyl- and epsilon-N-ethyl-lysine residues, and with acetic anhydride to form epsilon-N-acetyl-lysine residues, and made antibodies against these modified proteins in guinea-pigs. In ELISA assays antibodies made against methylated apoB-100 (Me-apoB) cross-reacted effectively with ethylated apoB-100 (Et-apoB), while antibodies made against acetic anhydride-modified apoB-100 did not cross-react. We conclude that methyl-lysine shares one or more immunoreactive epitopes with ethyl-lysine, and that antibodies which recognize acetaldehyde-modified proteins can be formed in response to formaldehyde-modified proteins. We demonstrate that sera from both alcoholics and non-drinkers contain antibodies which recognize Me-apoB and Et-apoB and that the titres of these antibodies are comparable. These data raise the possibility that some human serum antibodies which recognize acetaldehyde-modified protein epitopes may have been made against formaldehyde-modified protein epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1980

Breath acetaldehyde: evidence of acetaldehyde production by oropharynx microflora and by lung microsomes.

After alcohol ingestion, acetaldehyde is found in expired air and is thought to originate from blood. However, we found that the ratio of acetaldehyde to ethanol was higher in dead space than in alveolar (end-expiratory) air. This observation suggested production of acetaldehyde in the airways. To study this, we washed the mouth of normal subjects with 10 ml of either saline or 5 mM ethanol. Washings with ethanol produced 5.1 +/- 1.3 nmol/ml of acetaldehyde per minute (vs none with saline). Saline mouth washings incubated with ethanol produced acetaldehyde. This reaction could be prevented by boiling or by microfiltration of the washings suggesting that it was due to microbial enzymes of the oropharynx. We also studied the possibility of pulmonary production of acetaldehyde. Rat lung slices produced 1.32 +/- 0.19 mnol of acetaldehyde/g lung (wet weight)/minute; microsomal production of acetaldehyde was also detected and this was enhanced by chronic ethanol feeding.

Acetaldehyde↗