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M Salaspuro

Publications and source records attributed to M Salaspuro.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ciprofloxacin decreases the rate of ethanol elimination in humans.

BACKGROUND: Extrahepatic ethanol metabolism is postulated to take place via microbial oxidation in the colon, mediated by aerobic and facultative anaerobic bacteria. AIMS: To evaluate the role of microbial ethanol oxidation in the total elimination rate of ethanol in humans by reducing gut flora with ciprofloxacin. METHODS: Ethanol was administered intravenously at the beginning and end of a one week period to eight male volunteers. Between ethanol doses volunteers received 750 mg ciprofloxacin twice daily. RESULTS: A highly significant (p=0.001) reduction in the ethanol elimination rate (EER) was detected after ciprofloxacin medication. Mean (SEM) EER was 107.0 (5.3) and 96.9 (4.8) mg/kg/h before and after ciprofloxacin, respectively. Faecal Enterobacteriaceae and Enterococcus sp. were totally absent after medication, and faecal acetaldehyde production capacity was significantly (p<0.05) decreased from 0.91 (0.15) to 0.39 (0.08) nmol/min/mg protein. Mean faecal alcohol dehydrogenase (ADH) activity was significantly (p<0. 05) decreased after medication, but ciprofloxacin did not inhibit human hepatic ADH activity in vitro. CONCLUSIONS: Ciprofloxacin treatment decreased the ethanol elimination rate by 9.4%, with a concomitant decrease in intestinal aerobic and facultative anaerobic bacteria, faecal ADH activity, and acetaldehyde production. As ciprofloxacin has no effect on liver blood flow, hepatic ADH activity, or cytochrome CYP2E1 activity, these effects are probably caused by the reduction in intestinal flora.

Acetaldehyde↗
PubMed1999

Role of yeasts in the salivary acetaldehyde production from ethanol among risk groups for ethanol-associated oral cavity cancer.

BACKGROUND: Acetaldehyde, the first metabolite of alcohol, has been proposed to be the carcinogenic substance behind ethanol-related oral cancers. High levels of acetaldehyde are formed from ethanol in saliva by the oral flora, but so far the role of certain microbial species responsible for this phenomenon is not known. Yeasts are common commensals of the oral cavity that have alcohol-oxidizing enzymes, thus providing a potential source of acetaldehyde from ethanol. The aim of this study was to examine the contribution of oral yeasts to the production of ethanol-derived acetaldehyde in the oral cavity. METHODS: Fifty-five saliva samples were divided into two groups, high and low, based on the in vitro salivary acetaldehyde production capacity from ethanol. Yeasts were isolated and identified from these samples, and their acetaldehyde production capacity was determined gas chromatographically by incubating intact cells with ethanol at the physiological pH of 7.4. RESULTS: Yeast colonization was found in 78% of the high acetaldehyde-producing salivas, compared with 47% in the low acetaldehyde-producing salivas (p = 0.026). Among carriers, the density of yeasts was higher in the high than in low acetaldehyde producers (p = 0.025). Candida albicans was the main species isolated (88% of all oral isolates). Moreover, C. albicans strains isolated from the high acetaldehyde-producing salivas formed significantly higher acetaldehyde levels from ethanol than C. albicans strains from low-acetaldehyde-producing salivas (73.1 nmol ach/10e6 colony-forming units vs. 43.2 nmol ach/10e6 colony-forming units, p = 0.035). CONCLUSIONS: This study shows that some C. albicans strains have a marked capacity to produce toxic and carcinogenic acetaldehyde from ethanol in vitro. Because the in vitro production of salivary acetaldehyde has been previously shown to correlate with in vivo acetaldehyde production, our finding could be an important microbial pathogenetic factor underlying cancer of the oral cavity associated with ethanol drinking.

Acetaldehyde↗
PubMed1998

Effects of Triton WR 1339 and orotic acid on biliary and serum dolichols in rats.

Two lysosomal storage diseases, aspartylglucosaminuria and mannosidosis, are associated with highly elevated serum dolichol concentrations. To elucidate possible mechanisms leading to elevated serum dolichols, we studied the effects of Triton WR 1339 (known to increase serum cholesterol) and orotic acid (known to decrease serum cholesterol) on blood and biliary dolichol and beta-hexosaminidase levels in rats. In Triton WR 1339-treated rats, serum dolichol was markedly increased compared with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85 +/- 11 ng/mL, n = 8, P < .001), 4 (789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL, n = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P < .001) days after administration of the drug. By contrast, serum dolichol was decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7-day orotic acid feeding compared with controls. Serum beta-hexosaminidase was unaffected by both treatments. Orotic acid also increased biliary dolichol (280 +/- 47 ng/100 g body weight [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P < .01) and beta-hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g BW/h, n = 9, P < .01) excretion compared with controls. Thus, both Triton WR 1339 and orotic acid have an effect on dolichol metabolism, and it is conceivable--based on our results--that serum dolichol concentrations are regulated, at least in part, by a mechanism similar to that for serum cholesterol levels.

Animals↗
PubMed1998

Acetaldehyde alters proliferation, differentiation and adhesion properties of human colon adenocarcinoma cell line Caco-2.

Studies with experimental animals indicate that acetaldehyde, the first metabolite of ethanol that is microbially formed in the colonic lumen, may play a role in ethanol-associated colorectal co-carcinogenesis. Although intracoIonic acetaldehyde concentrations are highest during the metabolism of exogenous ethanol, some individuals may also possess marked amounts of endogenous acetaldehyde. Since no information is available concerning the possible effects of acetaldehyde on human colonic epithelial cells, this study was aimed to assess whether this compound, either alone or in combination with ethanol, affects such properties of human neoplastic colonocytes that are considered relevant with regard to cancer development. Human colon adenocarcinoma cell line Caco-2 was used as a model of transformed colonocytes, and effects of acetaldehyde and/or ethanol on the proliferation and differentiation of these cells as well as on their adhesion to collagens I and IV, the most important extracellular matrix proteins in the colon, were studied. The results of this study show that acetaldehyde markedly affects the phenotype of Caco-2 cells without having direct cytotoxic effects. Like many carcinogens, it was found to have a dual effect on cell proliferation rate, acute exposure being inhibitory and chronic exposure stimulating. Acetaldehyde also considerably decreased both sucrase activity and nuclear content of protein kinase A catalytic subunit in Caco-2 cells, which indicate that the differentiation of the cells was disturbed. Moreover, the adhesion of Caco-2 cells to collagens I and IV was dose-dependently reduced by acetaldehyde treatment. All these changes, i.e. enhanced cell proliferation rate (by chronic treatment), decreased differentiation, and reduced adhesion to extracellular matrix proteins, would in vivo predict more aggressive and invasive tumour behaviour. The possibility that colonic intraluminal acetaldehyde, either ethanol-derived or endogenous, might enhance the development of colorectal tumours should therefore be considered.

Acetaldehyde↗
PubMed1998

Flavodoxin-dependent pyruvate oxidation, acetate production and metronidazole reduction by Helicobacter pylori.

Helicobacter pylori flavodoxin was purified to homogeneity from cell extracts of strain NCTC 11637. The molecular weight of the protein was estimated by gel electrophoresis to be 18 kDa. Oxidized flavodoxin showed an absorption spectrum with maxima at 378 nm and 453 nm, and it was reduced to a neutral form of flavin semiquinone by the electrons generated in the oxidation of pyruvate. This coenzyme A dependent pyruvate:flavodoxin oxidoreductase activity of H. pylori was also detected as a reduction of methyl viologen or cytochrome c by bacterial extracts. The apparent Km of pyruvate was 310 microM. Anaerobically incubated bacteria (10[9]) of strain NCTC 11637 produced acetate (96 +/- 16 nmol/h) from pyruvate concomitantly reducing metronidazole (17 +/- 5 nmol/h). In anaerobic conditions both sensitive and resistant H. pylori strains reduced metronidazole, and there was a significant positive correlation between acetate production and metronidazole activation (r = 0.77, P < 0.01, n = 11). In the presence of atmospheric oxygen, H. pylori excreted twice as much acetate but metronidazole was not activated. These results suggest that the pyruvate:flavodoxin oxidoreductase complex catalyses pyruvate oxidation in H. pylori. Electrons generated in this reaction are transferred to flavodoxin and under anaerobic conditions further to metronidazole (imidazoles) thus reducing the drug to its bactericidal form.

Acetates↗
PubMed1998

Effect of alcohol on exercise-induced changes in serum glucose and serum free fatty acids.

The effect of alcohol on exercise-induced changes in serum glucose, serum free fatty acids, and serum insulin was studied in healthy male volunteers by performing an exhaustive ergometer exercise: (1) followed by alcohol intoxication (induced by 1.5 g of alcohol/kg of body weight); (2) during alcohol intoxication (induced by 0.8 g of alcohol/kg of body weight); and (3) during hangover (13 hr after a dose of 1.5 g of alcohol/kg of body weight). Acute alcohol intake immediately before exercise inhibited the exercise-induced increase in mean serum glucose concentration and caused a mild decrease in serum glucose levels during recovery from exercise. Exercise during hangover also resulted in decreased glucose levels during recovery from exercise. Alcohol administration immediately before or after exercise inhibited the postexercise increase in mean serum free fatty acids concentration. This was not seen during hangover, when blood alcohol concentration had already reached 0. In conclusion, alcohol interferes with the metabolism of carbohydrates during and after anaerobic exercise by decreasing the availability of circulating glucose. Furthermore, during recovery from exercise, alcohol decreases the supply of free fatty acids for the body.

Adult↗
PubMed1998

Role of catalase in in vitro acetaldehyde formation by human colonic contents.

Ingested ethanol is transported to the colon via blood circulation, and intracolonic ethanol levels are equal to those of the blood ethanol levels. In the large intestine, ethanol is oxidized by colonic bacteria, and this can lead to extraordinarily high acetaldehyde levels that might be responsible, in part, for ethanol-associated carcinogenicity and gastrointestinal symptoms. It is believed that bacterial acetaldehyde formation is mediated via microbial alcohol dehydrogenases (ADHs). However, almost all cytochrome-containing aerobic and facultative anaerobic bacteria possess catalase activity, and catalase can, in the presence of hydrogen peroxide (H2O2), use several alcohols (e.g., ethanol) as substrates and convert them to their corresponding aldehydes. In this study we demonstrate acetaldehyde production from ethanol in vitro by colonic contents in a reaction catalyzed by both bacterial ADH and catalase. The amount of acetaldehyde produced by the human colonic contents was proportional to the ethanol concentration, the amount of colonic contents, and the length of incubation time, even in the absence of added nicotinamide adenine dinucleotide or H2O2. The catalase inhibitors sodium azide and 3-amino-1,2,4-triazole (3-AT) markedly reduced the amount of acetaldehyde produced from 22 mM ethanol in a concentration dependent manner compared with the control samples (0.1 mM sodium azide to 73% and 10 mM 3-AT to 67% of control). H2O2 generating system [beta-D(+)-glucose + glucose oxidase] and nicotinamide adenine dinucleotide induced acetaldehyde formation up to 6- and 5-fold, respectively, and together these increased acetaldehyde formation up to 11-fold. The mean supernatant catalase activity was 0.53+/-0.1 micromol/min/mg protein after the addition of 10 mM H2O2, and there was a significant (p < 0.05) correlation between catalase activity and acetaldehyde production after the addition of the hydrogen peroxide generating system. Our results demonstrate that colonic contents possess catalase activity, which probably is of bacterial origin, and indicate that in addition to ADH, part of the acetaldehyde produced in the large intestine during ethanol metabolism can be catalase dependent.

Acetaldehyde↗
PubMed1998

Inhibition of intracolonic acetaldehyde production and alcoholic fermentation in rats by ciprofloxacin.

Heavy drinking is associated with many gastrointestinal symptoms and diseases, such as rapid intestinal transit time, diarrhea, colon polyps, and colorectal cancer. Acetaldehyde produced from ethanol by intestinal microbes has recently been suggested to be one of the pathogenetic factors related to alcohol-associated gastrointestinal morbidity. Furthermore, acetaldehyde is absorbed from the colon into portal blood and may thus contribute to the development of alcoholic liver injury. The present study was aimed to investigate the significance of gut aerobic flora in intracolonic acetaldehyde formation. For this study, 58 male Wistar rats (aged 9 to 11 weeks) were used. Half of the rats received ciprofloxacin for four consecutive days. Control rats (n = 29) received standard chow. On the fifth day of treatment, 1.5 g/kg body weight of ethanol was administered intraperitoneally to 19 rats receiving ciprofloxacin and 19 control rats. Ten ciprofloxacin-treated and 10 control rats received equal volumes of physiological saline intraperitoneally. Two hours after the injection of ethanol or saline, the samples of colonic contents and blood were obtained. Acetaldehyde and ethanol levels of the samples were determined by headspace gas chromatography. The intracolonic acetaldehyde level 2 hr after ethanol administration was 483+/-169 microM (maximum: 2.7 mM). High intracolonic acetaldehyde after ethanol injection was significantly reduced by ciprofloxacin treatment. After ciprofloxacin, intracolonic acetaldehyde levels before and after the injection of ethanol were 25+/-4.8 and 23+/-15 microM, respectively. Ciprofloxacin treatment resulted also in significantly higher blood (p < 0.005) and intracolonic (p < 0.0001) ethanol levels than in the control animals. Furthermore, ciprofloxacin treatment totally abolished the formation of endogenous ethanol in the large intestine. This study demonstrates that alcoholic fermentation and intracoIonic acetaldehyde production can be blocked by diminishing the amount of intracolonic aerobic bacteria with ciprofloxacin. Our findings indicate that the bacteriocolonic pathway for ethanol oxidation is mediated almost exclusively by gut aerobic microbes, and this knowledge may provide new insights into the studies on the pathogenesis of alcohol-related gastrointestinal symptoms and diseases.

Acetaldehyde↗
PubMed1997

Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa.

BACKGROUND: The tumor-promoting effect of ethanol on cancer of the upper respiratory-digestive tract is not well understood. Although ethanol itself is not carcinogenic, the first product of ethanol metabolism-acetaldehyde is. Acetaldehyde can be produced from ethanol by oral bacteria, and high concentrations have been observed in human saliva after ethanol consumption. The purpose of this study was to investigate whether acetaldehyde administered orally to rats induces altered differentiation and proliferation in the animals' upper gastrointestinal tracts. METHODS: Twenty Wistar rats were given either water containing acetaldehyde at a concentration of 120 mM or tap water to drink for 8 months. Tissue specimens were then taken from the tongue, epiglottis, and forestomach of each animal and immunohistochemically stained for markers of cellular proliferation (Ki67 nuclear antigen) or differentiation (cytokeratins 1, 4, 10, 11, 14, and 19). The mean epithelial thickness of each sample was measured via light microscopy, using an eyepiece containing grid lines. Differences between the control and acetaldehyde-treated groups were analyzed by use of the unpaired Student's t test. All reported P values are two-sided. RESULTS: Although no tumors were observed, staining for cytokeratins 4 and 14 revealed an enlarged basal layer of squamous epithelia in the rats receiving acetaldehyde. In these animals, cell proliferation was significantly greater than that observed in the control animals for samples from the tongue (P<.0001), epiglottis (P<.001), and forestomach (P<.0001). In addition, the epithelia from acetaldehyde-treated rats were significantly thicker than in epithelia from control animals (P<.05 for all three sites). CONCLUSIONS: Acetaldehyde, administered orally to rats, can cause hyperplastic and hyperproliferative changes in epithelia of the upper gastrointestinal tract. This finding suggests that microbially produced acetaldehyde in saliva may explain the tumor-promoting effect of ethanol on these epithelia.

Acetaldehyde↗
PubMed1997

Biliary excretion of dolichols and beta-hexosaminidase--effect of ethanol and glucagon.

Alcohol has been reported to increase the urinary excretion of dolichols, and urinary dolichols are suggested to be derived from the lysosomes of the renal cells. In the present study we examined the effects of alcohol and glucagon on the biliary excretion of dolichols in rats. Chronic ethanol treatment decreased both biliary dolichol and beta-hexosaminidase excretion. The absolute amount of dolichol excreted into the bile correlated highly significantly with the absolute amount of biliary beta-hexosaminidase. Our results indicate that biliary dolichols are--at least in part--derived from hepatic lysosomes. Decreased biliary dolichol output during chronic alcohol administration suggests that urinary and biliary dolichol excretions are regulated independently of each other.

Animals↗
PubMed1997

Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation.

Acetaldehyde, the first product of ethanol metabolism, has previously been shown to form potentially harmful adducts with various proteins. The aim of this study was to investigate whether acetaldehyde--either exogenous or metabolically derived--binds to gastric mucosal proteins. Homogenized rat gastric mucosa was incubated with various concentrations of radiolabeled acetaldehyde or ethanol for different time periods. Acetaldehyde-protein adducts were determined by a liquid scintillation counter. In addition, mucosa was incubated with nonlabeled ethanol, and the acetaldehyde formed was measured by using headspace gas chromatography. Incubation of gastric mucosa with (14C)-acetaldehyde led to a concentration- and time-dependent radiolabeling of mucosal proteins. Formation of acetaldehyde adducts occurred relatively rapidly within 30 minutes and even at low acetaldehyde levels (5 micromol/L). Stable adducts represented 77% +/- 5% (mean +/- SEM) of the total adducts formed. In the presence of ethanol, acetaldehyde production and adduct formation took place in a concentration- and time-dependent manner. 4-Methylpyrazole and sodium azide inhibited acetaldehyde production to 7% +/- 1% of control and decreased the amount of acetaldehyde adducts to 55% +/- 8%. Enhanced acetaldehyde formation (to 420% +/- 50%) was clearly reflected in increased adduct formation (550% +/- 110%). In conclusion, both exogenous and endogenous acetaldehyde binds to gastric mucosal proteins in vitro. Gastric mucosal acetaldehyde production and the consequent adduct formation could be a pathogenetic factor behind ethanol-associated gastric injury.

Acetaldehyde↗
PubMed1997

Inhibition of bacteriocolonic pathway for ethanol oxidation by ciprofloxacin in rats.

Many colonic bacteria possess marked alcohol dehydrogenase (ADH) activity and are capable of oxidizing ethanol to acetaldehyde both in vitro and in vivo. We have recently shown that part of ingested ethanol is metabolized to acetaldehyde in the colon during normal alcohol metabolism. To assess the contribution of this bacteriocolonic pathway for ethanol oxidation to total ethanol metabolism, the elimination rate of ethanol, faecal aerobic flora and faecal ADH activity were determined in rats before and after the treatment with ciprofloxacin (200 mg/kg/day) for four days. Ciprofloxacin treatment decreased ethanol elimination rate from 310+/-9 to 282+/-13 mg/kg/h (mean+/-SE; p<0.02), markedly reduced faecal aerobic flora, and also lowered faecal ADH activity from 63+/-17 to 17+/-7 nmol/min/mg faeces (p<0.05). Neither hepatic ADH nor microsomal ethanol oxidizing system activities were affected by the ciprofloxacin treatment. On the contrary, an acute intraperitoneal dose of ciprofloxacin had no effect on the rate of ethanol elimination. These results support the significant role of the bacteriocolonic pathway in total ethanol elimination, and open a new, microbiological, perspective for studies on ethanol metabolism and pathogenesis of alcohol related organ damages.

Alcohol Dehydrogenase↗
PubMed1997

High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications.

Chronic ethanol ingestion leads to an enhanced risk of upper gastrointestinal tract cancer. Although many hypotheses for the tumor promoting effect of alcohol exist, the pathogenetic mechanisms remain unclear since alcohol in itself is not carcinogenic. Acetaldehyde, the first metabolite of ethanol, has been shown to have multiple mutagenic effects and to be carcinogenic to animals. Previous research has revealed that acetaldehyde can be formed from ethanol via microbial alcohol dehydrogenase. Thus, at least part of the proposed tumorigenic effect of ethanol may be linked to local production of acetaldehyde from ethanol by oral microflora. In this study we demonstrate the production of marked amounts of acetaldehyde in saliva after ingestion of moderate amounts of ethanol. Considerable inter individual variation in acetaldehyde production capacity is also shown. In vivo acetaldehyde production is significantly reduced after a 3-day use of an antiseptic mouthwash (chlorhexidine). In vitro acetaldehyde production was shown to be linear in time, inhibited by 4-methylpyrazole and it could not be saturated under ethanol conditions that are relevant in vivo. There was a significant positive correlation between salivary acetaldehyde production in vitro and in vivo. We conclude, that the microbial formation of acetaldehyde in saliva could be one explanation for the tumor promoting effect of ethanol on the upper gastrointestinal tract. Moreover, this may support the epidemiological finding, that poor oral hygiene is an independent risk factor for oral cavity cancer.

Acetaldehyde↗
PubMed1997

Allelic association between D2 but not D1 dopamine receptor gene and alcoholism in Finland.

We studied the relationship of D2 and D1 receptor gene polymorphisms and alcoholism in male Finnish alcoholics and assessed male controls. Seventy alcoholics entering a detoxification programme and 50 control individuals were recruited. Forty-three per cent of the alcoholic patients, but only 22% of controls, had the D2 receptor gene TaqI A restriction fragment length polymorphism A1 allele. The frequency of the A1 allele was significantly higher in alcoholics (p = 0.039). In comparison, no association between alcoholism and the D1 receptor gene EcoRI restriction fragment length polymorphism alleles was found. A logistic regression analysis of the alcoholic population failed to support the idea that the presence of the A1 allele would be linked to estimates of alcohol dependence severity rated with the Severity of Alcohol Dependence Questionnaire or the Michigan Alcoholism Screening Test. In conclusion, allelic association between the D2 but not D1 receptor gene and alcoholism in a genetically relatively homogenous population of male Finns was found. The results are in agreement with the view that the D2 receptor locus is involved in genetic susceptibility to alcoholism but does not give support to a special association of severe alcohol dependence and the A1 allele of the D2 receptor gene.

Alcoholism↗
PubMed1997

Characteristics of alcohol dehydrogenases of certain aerobic bacteria representing human colonic flora.

We have recently proposed the existence of a bacteriocolonic pathway for ethanol oxidation [i.e., ethanol is oxidized by alcohol dehydrogenases (ADHs) of intestinal bacteria resulting in high intracolonic levels of reactive and toxic acetaldehyde]. The aim of this in vitro study was to characterize further ADH activity of some aerobic bacteria, representing the normal human colonic flora. These bacteria were earlier shown to possess high cytosolic ADH activities (Escherichia coli IH 133369, Klebsiella pneumoniae IH 35385, Klebsiella oxytoca IH 35339, Pseudomonas aeruginosa IH 35342, and Hafnia alvei IH 53227). ADHs of the tested bacteria strongly preferred NAD as a cofactor. Marked ADH activities were found in all bacteria, even at low ethanol concentrations (1.5 mM) that may occur in the colon due to bacterial fermentation. The Km for ethanol varied from 29.9 mM for K. pneumoniae to 0.06 mM for Hafnia alvei. The inhibition of ADH by 4-methylpyrazole was found to be of the competitive type in 4 of 5 bacteria, and Ki varied from 18.26 +/- 3.3 mM for Escherichia coli to 0.47 +/- 0.13 mM for K. pneumoniae. At pH 7.4, ADH activity was significantly lower than at pH 9.6 in four bacterial strains. ADH of K. oxytoca, however, showed almost equal activities at neutral pH and at 9.6. In conclusion, NAD-linked alcohol dehydrogenases of aerobic colonic bacteria possess low apparent Km's for ethanol. Accordingly, they may oxidize moderate amounts of ethanol ingested during social drinking with nearly maximal velocity. This may result in the marked production of intracolonic acetaldehyde. Kinetic characteristics of the bacterial enzymes may enable some of them to produce acetaldehyde even from endogenous ethanol formed by other bacteria via alcoholic fermentation. The microbial ADHs were inhibited by 4-methylpyrazole by the same competitive inhibition as hepatic ADH, however, with nearly 1000 times lower susceptibility. Individual variations in human colonic flora may thus contribute to the risk of alcohol-related gastrointestinal morbidity, such as diarrhea, colon polyps and cancer, and liver injury.

Acetaldehyde↗
PubMed1997

Effects of acetaldehyde on brush border enzyme activities in human colon adenocarcinoma cell line Caco-2.

The treatment of Caco-2 cells, a human colon adenocarcinoma cell line that closely resembles normal human small intestinal epithelial cells, with acetaldehyde resulted in significantly decreased activities of brush border enzymes sucrase, maltase, lactase, and gamma-glutamyltransferase; alkaline phosphatase activity was not affected. In the case of sucrase and maltase, the activities were also decreased by a combination of acetaldehyde and ethanol, although ethanol alone markedly increased them. The possibility that intraintestinal acetaldehyde, formed by intestinal microbes, might play a role in some small intestinal enzyme deficiencies observed earlier in alcoholics should therefore be considered. The mechanism by which acetaldehyde alters these enzyme activities remains unclear. The observation that acetaldehyde also disturbed cell polarization, an initial step in the process of differentiation in Caco-2 cells, indicates that acetaldehyde might decrease these enzyme activities by interfering with cell differentiation. Because ethanol and acetaldehyde metabolizing enzymes have not been previously studied from Caco-2 cells, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were also measured from these cells, and their ALDH isoenzyme pattern was characterized. Like many cancerous cell lines, Caco-2 cells were found to express no ADH. They, however, possessed ALDH activity that was comparable with normal colonic mucosal activity and also expressed the same ALDH classes (ALDHs 1 to 3) than normal human colonic mucosa.

Acetaldehyde↗
PubMed1996

Hepatotoxicity and absorption of extrahepatic acetaldehyde in rats.

Acetaldehyde, the first metabolite of ethanol oxidation, has been proposed as a major initiating factor in ethanol-induced liver injury. The aims of this study were to examine whether acetaldehyde is absorbable from the digestive tract and whether, when delivered chronically in drinking water, it is capable of inducing liver injury in rats. Acetaldehyde concentrations in the rat portal and peripheral blood were measured by head space gas chromatography after intragastric (5 ml) and intracolonic (3 ml) administration of 20 mM acetaldehyde solution. In the hepatotoxicity study, rats were exposed to acetaldehyde (20 and 120 mM) delivered in drinking water for 11 weeks and histopathological changes in the liver were morphometrically assessed. Peak blood acetaldehyde levels were found at 5 min after acetaldehyde infusion and were 235 +/- 11 microM (mean +/- SE) after intragastric and 344 +/- 83 microM after intracolonic infusion of 20 mM acetaldehyde solution. The exposure of rats to 120 mM acetaldehyde solution for 11 weeks resulted in the development of fatty liver and inflammatory changes. Morphometric analysis showed significantly more fat accumulation in rats receiving 120 mM acetaldehyde solution (85 +/- 2 per cent of hepatocytes occupied by fat) than in rats receiving 20 mM acetaldehyde solution (38 +/- 11 per cent) or in controls (36 +/- 10 per cent). The dose of extrahepatic acetaldehyde (500 mg/kg per day) producing liver injury corresponds to only around 3 per cent of that derived from hepatic ethanol oxidation in animals receiving an ethanol-containing totally liquid diet (15 g/kg per day). These results indicate that acetaldehyde delivered via the digestive tract can reach the liver by the portal circulation and that acetaldehyde of extrahepatic origin appears to be more hepatotoxic than acetaldehyde formed during ethanol oxidation within the liver.

Absorption↗