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 271 records · Page 15Linked to original sources
PubMed2002

Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine.

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL(95%) 43%, 76%). Area under the curve (AUC(0-320min)) with the L-cysteine and placebo tablet were 54.3 +/- 11 microM x hr and 162 +/- 34.2 microM x hr (mean +/- SEM), respectively (p = 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow-releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals.

Acetaldehyde↗
PubMed2004

Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva.

Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3-day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114.8 +/- 11.5 vs. 54.2 +/- 8.7 microM x hr, respectively; p = 0.002). Secondly, smokers with active smoking during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels than nonsmokers (AUC 369.5 +/- 12.2 vs. 54.2 +/- 8.7 microM x hr, respectively; p < 0.001). We conclude that this markedly increased exposure of upper digestive tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking subjects may explain the synergistic and multiplicative risk effect of alcohol drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis.

Acetaldehyde↗
PubMed1986

Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats.

The effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4-week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3-h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold. Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound-related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde or interruptedly exposed to 110 ppm with peak loads of 660 ppm. As a consequence 150 ppm acetaldehyde can be considered a 'no-toxic-effect level' in male rats exposed for 6 h/day, 5 days/week, during a 4-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1998

Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in rat Kupffer cells.

BACKGROUND AND AIMS: Treatment with acetaldehyde dehydrogenase inhibitors leads to increased liver acetaldehyde levels and prevents hepatic inflammation and necrosis in ethanol-fed rats. This is accompanied by IkappaBa preservation and decreased activation of nuclear factor (NF)-kappaB. The present in vitro study was aimed to clarify whether acetaldehyde has an effect on degradation of IkappaBalpha and activation of NF-kappaB in LPS-stimulated rat Kupffer cells. METHODS: Kupffer cells were isolated from male Sprague-Dawley rats and preincubated with various concentrations of acetaldehyde (25-100 microM). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. IkappaBalpha and p65 proteins and activation of NF-kappaB were evaluated. RESULTS: In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of IkappaBalpha, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-kappaB activation. CONCLUSIONS: Acetaldehyde is clearly involved in the stabilization of IkappaBalpha protein and suppression of NF-kappaB activation in rat Kupffer cells. Acetaldehyde may form an adduct with IkappaBalpha, thus making the protein less susceptible to degradation.

Acetaldehyde↗
PubMed1977

Regulatory factors of acetaldehyde metabolism in isolated rat liver mitochondria.

The factors affecting acetaldehyde oxidation were studied by direct measurement of redox changes of NADH and cytochrome c in isolated rat liver mitochondria which contain the natural complement of mitochondrial substrates and co-factors, etc. Thus, this system affords a quantitative model for mitochondrial acetaldehyde metabolism simulating in vivo conditions. The activity of acetaldehyde dehydrogenase, as measured by the turnover number of cytochrome c, k3, depends upon the substrate concentration in a complex way. It reaches a maximum below 0.033 mM acetaldehyde and decreases abruptly at higher acetaldehyde concentration, interpreted here to be due to substrate inhibition. When mitochondria undergo hypotonic swelling, the maximal value of k3 is lowered by a factor of 15 and the substrate inhibition largely disappears. When mitochondria are stripped of the outer membrane and are suspended in pyrophosphate buffer, similar effects are obtained. It is concluded that acetaldehyde oxidation in mitochondria is dependent upon the state of mitochondria and the substrate concentration, and that the mitochondrial metabolism of acetaldehyde cannot be accurately predicted from in vitro data of solubilized enzyme.

Acetaldehyde↗
PubMed1985

Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown by gamma-glutamyltranspeptidase.

Glutathione and its metabolites were examined for reactivity to acetaldehyde. When acetaldehyde was incubated with glutathione alone, there was only a slight decrease of acetaldehyde, while an apparently equimolar reaction between acetaldehyde and free sulfhydryl was observed with the addition of gamma-glutamyltranspeptidase. Cysteinylglycine, the first metabolite in the glutathione breakdown by gamma-glutamyltranspeptidase, showed a rapid and equimolar reactivity to acetaldehyde and such was comparable to the reaction seen with L-cysteine or D-penicillamine. In light of the chemical structure, cysteinylglycine probably conjugates with acetaldehyde to form thiazolidinecarboxylic acid derivatives, 2-methyl-thiazolidine-4-carbonyl-glycine, and if so, the alteration of glutathione metabolism by acetaldehyde during ethanol intoxication warrants further attention.

Acetaldehyde↗
PubMed2004

Acetaldehyde accumulation suppresses Kupffer cell release of TNF-Alpha and modifies acute hepatic inflammation in rats.

BACKGROUND: Alcohol-related diseases have multiple and varied associations with acetaldehyde, a highly toxic product of ethanol oxidation that accumulates in the absence of active aldehyde dehydrogenase (ALDH). This study was designed to clarify the role of acetaldehyde in liver injury, specifically in vivo and in vitro effects on Kupffer cell release of the inflammatory cytokine tumor necrosis factor-alpha (TNF-Alpha). METHODS: Rats pretreated overnight with the ALDH inhibitor disulfiram (or saline control) were ethanol loaded and challenged with lipopolysaccharide (LPS), and their blood and histological parameters were examined 3 h later. Similarly, isolated rat Kupffer cells were pretreated with disulfiram or cyanamide incubated in ethanol (1 h), then challenged with LPS and evaluated 2 h later for TNF-Alpha and acetaldehyde levels in the culture medium. TNF-Alpha release from Kupffer cells after LPS challenge was also evaluated following incubation in acetaldehyde and acetate for comparison with ethanol loading. RESULTS: Higher blood acetaldehyde concentration following disulfiram pretreatment significantly attenuated acute hepatic inflammation in the ethanol-loaded, LPS-challenged rat (18 +/- 2.9 vs 30 +/- 3.7 polymorphonuclear cells/portal area; P = 0.01). After LPS challenge, ALDH inhibitor pretreatment attenuated Kupffer cell release of TNF-Alpha in the presence of disulfiram at 5063 +/- 151 pg/ml and cyanamide at 4390 +/- 934 pg/ml, versus no inhibitor, 5869 +/- 265 pg/ml ( P < 0.01), but not in the absence of ethanol. Acetaldehyde significantly suppressed Kupffer cell TNF-Alpha release ( P < 0.05), but acetate treatment did not. CONCLUSIONS: Acetaldehyde accumulation suppresses macrophage function, at least suppressing TNF-Alpha release, which plays a role in modifying acute hepatic inflammation in rats.

Acetaldehyde↗
PubMed2004

Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones.

Ethanol consumption has long been associated with brain damage. However, the mechanism underlying this deleterious effect remains unclear. Among different hypotheses, acetaldehyde is regarded by certain authors as playing a major role in the expression of ethanol toxicity, but there are still some uncertainties about the exact nature of its implication. We therefore tried to characterize the profile of the alterations of neuronal viability and DNA integrity obtained after either a direct exposure to ethanol or to acetaldehyde. Ethanol at concentrations within the range of blood alcohol levels in intoxicated humans (< or = 100 mmol/L) induced DNA alterations without any apparent effect on cell viability. Acetaldehyde (< or = 1000 micromol/L) can also induce DNA alterations but with a different profile of the DNA cellular alterations. The comparison between the distributions of the comet tail DNA indicated that ethanol induced strong breaks (tail DNA > or = 60 a.u.) generation whereas acetaldehyde rather induced lower breaks (20 < or = tail DNA < or = 50 a.u.) formation but affecting a greater number of neurones. Acetaldehyde had thus a different genotoxic potential which may suggest a different mode of action or a different cellular target. Furthermore, when a single 100 mmol/L ethanol exposure did not lead to any loss of cell viability, the addition of an inhibitor of aldehyde dehydrogenase was followed by a significant loss in viability. In contrast, the inhibition of catalase, which suppresses acetaldehyde synthesis, led to no reduced viability in the same exposure conditions. ROS also reduced viability, but this was observed only after both cytochrome P450 stimulation and catalase inhibition. These combined results could suggest that acetaldehyde may play a significant role in the expression of ethanol toxicity in brain.

Acetaldehyde↗
PubMed2005

Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappaB signaling pathway in HepG2 cells.

Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), have been correlated with the patients affected by ALD. However, the direct effect of alcohol in the induction of IL-1beta and TNF-alpha has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1beta and TNF-alpha production in HepG2 cells. Nuclear factor-kappaB (NF-kappaB), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory kappaB-alpha (IkappaB-alpha) phosphorylation and degradation. However, the NF-kappaB inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-kappaB activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1beta and TNF-alpha production via the regulation of NF-kappaB signaling pathway. By screening 297 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we found that Coptis chinensis (Huang-Lien) and Phellodendron amurense (Huang-Po) were capable of inhibiting acetaldehyde-induced NF-kappaB activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappaB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IkappaB-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells. Our findings also suggested the potential role of berberine in the treatment of ALD.

Acetaldehyde↗
PubMed1984

Enhancement of acetaldehyde-protein adduct formation by L-ascorbate.

The effect of L-ascorbate on the binding of [14C]acetaldehyde to bovine serum albumin was examined. In the absence of ascorbate, acetaldehyde reacted with albumin to form both unstable (Schiff bases) and stable adducts. Ascorbate (5 mM) caused a time-dependent increase in the formation of total acetaldehyde-albumin adducts, which were comprised mainly of stable adducts. Significant enhancement of adduct formation by ascorbate was observed at acetaldehyde concentrations as low as 5 microM. An ascorbate concentration as low as 0.5 mM was still effective in stimulating stable adduct formation. The electron acceptor, 2,6 dichlorophenolindophenol, prevented the ascorbate-induced increase in albumin-adduct formation. Ascorbate also caused enhanced acetaldehyde adduct formation with other purified proteins, including cytochrome c and histones, as well as the polyamino acid, poly-L-lysine. These results indicate that ascorbate, acting as a reducing agent, can convert unstable acetaldehyde adducts to stable adducts, and can thereby increase and stabilize the binding of acetaldehyde to proteins.

2,6-Dichloroindophenol↗
PubMed1984

Inhibition of the oxidation of acetaldehyde and formaldehyde by hepatocytes and mitochondria by crotonaldehyde.

Crotonaldehyde was oxidized by disrupted rat liver mitochondrial fractions or by intact mitochondria at rates that were only 10 to 15% that of acetaldehyde. Although a poor substrate for oxidation, crotonaldehyde is an effective inhibitor of the oxidation of acetaldehyde by mitochondrial aldehyde dehydrogenase, by intact mitochondria, and by isolated hepatocytes. Inhibition by crotonaldehyde was competitive with respect to acetaldehyde, and the Ki for crotonaldehyde was about 5 to 20 microM. Crotonaldehyde had no effect on the oxidation of glutamate or succinate. Very low levels of acetaldehyde were detected during the metabolism of ethanol. Crotonaldehyde increased the accumulation of acetaldehyde more than 10-fold, indicating that crotonaldehyde, besides inhibiting the oxidation of added acetaldehyde, also inhibited the oxidation of acetaldehyde generated by the metabolism of ethanol. Formaldehyde was a substrate for the low-Km mitochondrial aldehyde dehydrogenase, as well as for a cytosolic, glutathione-dependent formaldehyde dehydrogenase. Crotonaldehyde was a potent inhibitor of mitochondrial oxidation of formaldehyde, but had no effect on the activity of formaldehyde dehydrogenase. In hepatocytes, crotonaldehyde produced about 30 to 40% inhibition of formaldehyde oxidation, which was similar to the inhibition produced by cyanamide. This suggested that part of the formaldehyde oxidation occurred via the mitochondrial aldehyde dehydrogenase, and part via formaldehyde dehydrogenase. The fact that inhibition by crotonaldehyde is competitive may be of value since other commonly used inhibitors of aldehyde dehydrogenase are irreversible inhibitors of the enzyme.

Acetaldehyde↗
PubMed1985

Aldehyde dehydrogenase activity as the rate-limiting factor for acetaldehyde metabolism in rat liver.

The velocity of acetaldehyde metabolism in rat liver may be governed either by the rate of regeneration of NAD from NADH through the electron transport system or by the activity of aldehyde dehydrogenase (ALDH). Measurements of oxygen consumption revealed that the electron transport system was capable of reoxidizing ALDH-generated NADH much faster than it was produced and hence was not rate-limiting for aldehyde metabolism. To confirm that ALDH activity was the rate-limiting factor, low-Km ALDH in slices or intact mitochondria was partially inhibited by treatment with cyanamide and the rate of acetaldehyde metabolism measured. Any inhibition of low-Km ALDH resulted in a decreased rate of acetaldehyde metabolism, indicating that no excess of low-Km ALDH existed. Approximately 40% of the metabolism of 200 microM acetaldehyde in slices was not catalyzed by low-Km ALDH. Fifteen of this 40% was catalyzed by high-Km ALDH. A possible contribution by aldehyde oxidase was ruled out through the use of a competitive inhibitor, quinacrine. Acetaldehyde binding to cytosolic proteins may account for the remainder. By measuring acetaldehyde accumulation during ethanol metabolism, it was also established that low-Km ALDH activity was rate-limiting for acetaldehyde oxidation during concomitant ethanol oxidation.

Acetaldehyde↗
PubMed1987

Covalent binding of acetaldehyde to tubulin: evidence for preferential binding to the alpha-chain.

The covalent binding of [14C]acetaldehyde to purified beef brain tubulin was characterized. As we have found for several other proteins, tubulin bound acetaldehyde to form both stable and unstable adducts. Unstable adducts (Schiff bases) were stabilized, and rendered detectable, by treating incubated reaction mixtures with the reducing agent sodium borohydride. In short-term incubations, the majority of the adducts formed were unstable, but the percentage of total adducts that were stable gradually increased with time. Stable adduct formation was greatly increased by the inclusion of sodium cyanoborohydride in reaction mixtures (reductive ethylation). When reaction mixtures were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis to separate the alpha- and beta-chains of the heterodimeric tubulin molecule, the alpha-chain of free tubulin, but not intact microtubules, was the preferential site of stable adduct formation under both reductive and nonreductive conditions. Denaturation studies showed that the native tubulin conformation was necessary for the alpha-chain to show enhanced reactivity toward acetaldehyde. Competition binding studies showed that alpha-tubulin could effectively compete with beta-tubulin and bovine serum albumin for a limited amount of acetaldehyde. Unstable acetaldehyde adducts with free tubulin or microtubules did not exhibit alpha-chain selectivity. Analysis of reaction mixtures indicates that lysine residues are the major group of the protein participating in adduct formation. These data indicate that the alpha-chain of free tubulin is the preferential site of stable acetaldehyde-tubulin adduct formation. Further, these data raise the possibility that alpha-tubulin may be a selective target for acetaldehyde adduct formation in cellular systems.

Acetaldehyde↗
PubMed1983

Ethanol oxidation in systems containing soluble and mitochondrial fractions of rat liver. Regulation by acetaldehyde.

Systems containing soluble fraction of rat liver, with or without mitochondrial fraction, oxidised [1-14C] ethanol to acetaldehyde, 14CO2 and non-volatile 14C-products of which acetate was the principal, and possibly the only, component. Ethanol oxidation was stimulated by pyruvate which served as an electron sink thereby allowing rapid regeneration of NAD. When no mitochondria were present acetaldehyde accumulated, rapidly at first but eventually reaching a plateau. The rate of ethanol oxidation in these systems was much lower than the measured maximum activity of alcohol dehydrogenase (ADH) and it was concluded that ADH was inhibited by the accumulated acetaldehyde. Mitochondria, because of their relatively high aldehyde dehydrogenase (ALDH) activity, prevented the accumulation of acetaldehyde, or quickly removed acetaldehyde already accumulated. This action was accompanied by a sharp increase in the rate of ethanol oxidation, presumably due to the deinhibition of ADH. Cyanamide, an inhibitor of mitochondrial ALDH, blocked the stimulatory effect of mitochondria on ethanol oxidation. It was concluded that, in the reconstituted systems, acetaldehyde played a dominant role in controlling the rate of ethanol oxidation. The possible importance of acetaldehyde in governing ethanol oxidation in vivo is discussed.

Acetaldehyde↗
PubMed1987

Blood acetaldehyde and the ethanol-induced increase in splanchnic circulation.

Acute oral administration of ethanol significantly increases (50-60%) portal blood flow to the liver. As earlier studies have indicated that this effect is maximal at concentrations of ethanol that saturate the alcohol dehydrogenase (ADH) system and is blocked by the ADH inhibitor 4-methylpyrazol, we investigated the possible role of acetaldehyde, a product in the ADH reaction, as a mediator of this effect. In the first series of experiments it was shown that, contrary to expectations, cyanamide administration prior to alcohol suppressed fully the effect of ethanol on portal blood flow without altering it in the absence of ethanol [ethanol = 69.5 +/- 5.6; ethanol + cyanamide 42.9 +/- 2.4; control = 43.0 +/- 3.0; cyanamide = 55.1 +/- 3.7 ml X min-1 X (kg body wt)-1]. Arterial blood concentrations of acetaldehyde were elevated from 3.6 +/- 0.3 microM in the presence of ethanol to 293 +/- 48 microM in the presence of ethanol + cyanamide. Infusion of acetaldehyde either into the left ventricle, resulting in arterial blood acetaldehyde levels of 227 +/- 77 microM, or into the portal circulation, resulting in arterial blood levels of 198 +/- 40 microM, did not modify portal blood flow or splanchnic hemodynamics, nor the effect of ethanol per se. The combination of cyanamide + ethanol significantly reduced total peripheral resistance (from 28 +/- 3 to 19 +/- 2 dyne X cm X sec-5), while neither ethanol or cyanamide per se, nor acetaldehyde affected total peripheral resistance. Data suggest that acetaldehyde is not involved in the ethanol-mediated increase in portal vein flow. Further studies indicate that the effects of cyanamide in suppressing the ethanol-induced increase in portal blood flow and increasing total peripheral resistance appear to be related to an ethanol-cyanamide interaction which is independent of the acetaldehyde levels in the circulation.

Acetaldehyde↗
PubMed1990

Possible role of acetaldehyde in ethanol-related rectal cocarcinogenesis in the rat.

Prospective epidemiologic studies have reported an increased risk of rectal cancer following chronic ethanol ingestion. The effect of ethanol on chemically induced colorectal carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic ethanol administration on acetoxymethylmethylnitrosamine-induced rectal cancer and the possible role of acetaldehyde in this process were investigated. Chronic ethanol administration resulted in an earlier occurrence of rectal tumors in this animal model. Because the concomitant administration of cyanamide, a potent acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of tumors, acetaldehyde could be involved in the ethanol-associated carcinogenesis. To measure colonic acetaldehyde, 12 chronically ethanol-fed and control rats received an acute dose of ethanol (2.5 g/kg body wt). The mucosal concentration of acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic ethanol feeding. Furthermore, 6 germ-free rats had significantly lower acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg protein-1, p less than 0.05). The data show that chronic ethanol ingestion accelerates chemically induced rectal carcinogenesis and raise the possibility that acetaldehyde probably generated through bacterial ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour carcinogenesis.

Acetaldehyde↗
PubMed1992

Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori.

We have recently shown that Helicobacter pylori possesses marked alcohol dehydrogenase (ADH) activity and is capable--when incubated with an ethanol containing solution in vitro--of producing large amounts of acetaldehyde. In the present study we report that some drugs commonly used for the eradication of H. pylori and for the treatment of gastroduodenal diseases are potent ADH inhibitors and, consequently, effectively prevent bacterial oxidation of ethanol to acetaldehyde. Colloidal bismuth subcitrate (CBS), already at a concentration of 0.01 mM, inhibited H. pylori ADH by 93% at 0.5 M ethanol and decreased oxidation of 22 mM ethanol to acetaldehyde to 82% of control. At concentrations above 5 mM, CBS almost totally inhibited acetaldehyde formation. Omeprazole, a drug also known to suppress growth of H. pylori, also inhibited H. pylori ADH and suppressed bacterial acetaldehyde formation significantly to 69% of control at a drug concentration of 0.1 mM. By contrast, the H2-receptor antagonists ranitidine and famotidine showed only modest effect on bacterial ADH and acetaldehyde production. We suggest that inhibition of bacterial ADH and a consequent suppression of acetaldehyde production from endogenous or exogenous ethanol may be a novel mechanism by which CBS and omeprazole exert their effect both on the growth of H. pylori as well as on H. pylori associated gastric injury.

Acetaldehyde↗
PubMed1988

A mutagenicity assessment of acetaldehyde.

Acetaldehyde has been shown in studies by several different laboratories to be a clastogen (chromosome-breaking) and inducer of sister-chromatid exchanges in cultured mammalian cells (Chinese hamster cells and human lymphocytes). Although there have been very few studies in intact mammals, the available evidence suggests that acetaldehyde produces similar cytogenetic effects in vivo. The production of cytogenetic abnormalities may be related to the ability of acetaldehyde to form DNA-DNA and/or DNA-protein cross-links. Acetaldehyde apparently has not been evaluated for its ability to cause gene mutations in cultured mammalian cells, but it has been shown to produce sex-linked recessive lethals in Drosophila. In general, bacteria tests have been negative. Although acetaldehyde is a genotoxic cross-linking agent, it does not appear to cause DNA strand breaks. There were no studies available regarding the potential of acetaldehyde to produce genetic damage in mammalian germ cells in vivo. Most mutagenicity testing on acetaldehyde has been motivated by attempts to define the proximate mutagen in ethanol metabolism.

Acetaldehyde↗