Lack of alcohol dehydrogenase isoenzyme activities in the stomach of Japanese subjects

Baraona, Enrique; Yokoyama, Akira; Ishii, Hiromasa; Hernández‐Muñoz, Rolando; Takagi, Toshikazu; Tsuchiya, Masaharu; Lieber, Charles S.

doi:10.1016/0024-3205(91)90295-m

Cited by 91 publications

(40 citation statements)

References 11 publications

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“…This is in accordance with the findings of Moreno and Pares [1] who estimated that approximately 30-50% of the mucosal ADH contributes to Û-ADH. It is noteworthy that the polymorphism of ADH 3 also influences significantly the total ADH activity [8,10]. Homozygous subjects with Á 2 Á 1 isozyme (ADH 1 3 phenotype) had higher gastric ADH activities as compared with heterozygous subjects (ADH 3 [1][2] ) and homozygous subjects with Á 2 Á 2 isozyme (ADH 2 3 ) [8,10].…”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that the polymorphism of ADH 3 also influences significantly the total ADH activity [8,10]. Homozygous subjects with Á 2 Á 1 isozyme (ADH 1 3 phenotype) had higher gastric ADH activities as compared with heterozygous subjects (ADH 3 [1][2] ) and homozygous subjects with Á 2 Á 2 isozyme (ADH 2 3 ) [8,10]. It has been shown that HP is capable to oxidize ethanol to acetaldehyde by ADH in vitro, and this metabolism has been claimed to play a role as pathogenic mechanism in HP-associated mucosal injury [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…The existence of FPM may explain the fact that following an oral dose of ethanol, blood ethanol concentrations are significantly lower than blood levels following intravenous administration of the same dose of ethanol [6,7]. Gastric ADH activity and FPM of ethanol are affected by various factors including gender [2,4], ethnology [8][9][10], age [4,11,12], medication [3,13,14], gastric morphology [15,16], and the concentration of ethanol in the alcoholic beverage [17,18]. Furthermore, FPM of ethanol is also influenced by the gastric emptying time [16,18].…”

Section: Introductionmentioning

confidence: 99%

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<i>Helicobacter pylori</i> Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man

et al. 1998

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Background/Aims: Ethanol is metabolized by alcohol dehydrogenase in the human stomach. This metabolism contributes to the so-called first-pass metabolism of ethanol which is affected by gender, medication, and morphological alterations of the gastric mucosa. Recently, it has been shown that Helicobacter pylori is capable to oxidize ethanol to acetaldehyde in vitro. Since H. pylori also injures gastric mucosa, the present study examines the effect of this bacterium on gastric alcohol dehydrogenase activity and systemic availability of ethanol in vivo. Methods: Thirteen volunteers (7 men and 6 women, aged 18–52 years) with gastric H. pylori infection diagnosed by a positive CLO test and positive gastric histology received ethanol (0.225 g/kg) either orally or intravenously before and after H. pylori elimination to determine systemic availability of ethanol. In addition, gastric biopsy specimens were taken from all subjects before and after H. pylori elimination for histological assessment of mucosal alterations and determinations of gastric alcohol dehydrogenase activity and phenotype of the enzyme. Results: In the presence of H. pylori the first-pass metabolism of ethanol was found to be significantly reduced (625 ± 234 vs. 1,155 ± 114 mg/dl/min, p = 0.046). This reduction of first-pass metabolism of ethanol was associated with a significant decrease in alcohol dehydrogenase activity (4.8 ± 1.5 vs. 12.1 ± 2.3 nmol/mg protein × min, p < 0.05) and an increase in the severity of mucosal damage as determined by a histological score (p < 0.05). Conclusions: H. pylori infection leads to gastric mucosal injury which is associated with a decrease in gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol. Ethanol metabolism by H. pylori does not play an important role in vivo. However, gastric morphology is one important factor determining systemic availability of ethanol in man.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<i>Helicobacter pylori</i> Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man

et al. 1998

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“…Among the various pharmacological treatments available for this disorder, disulfiram (Antabuse) is the oldest (Litten et al, 1996) and perhaps most widely utilized (Fuller and Roth, 1979;Chick et al, 1992). Its mechanism of action is thought to reside in its aldehyde-dehydrogenase-inhibiting property, through which it should raise acetaldehyde blood levels, produced by ethanol ingested and metabolized by alcohol-dehydrogenase, an enzyme normally found in the gastric and hepatic tissue of human beings (Baraona et al, 1991). In turn, the augmented blood acetaldehyde concentrations are considered to be peripherally aversive (Litten et al, 1996;Eriksson, 2001) and to form the basis for the well-known 'flushing syndrome', commonly observed after ethanol ingestion in many orientals, an ethnic group with a low incidence of alcoholism.…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

Foddai

Dosia

Spiga

et al. 2003

Neuropsychopharmacol

155

137

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Acetaldehyde is the first and principal metabolite of ethanol administered systemically. To its rise in blood, after administration of disulfiram, is ascribed the aversive reaction that should discourage alcoholics from drinking. In the present study, we sought to determine the effect of acetaldehyde on the electrophysiological properties of dopamine (DA)-containing neurons in the ventro tegmental area (VTA) of rats in vivo. Intravenous (i.v.) administration of acetaldehyde (5-40 mg/kg) readily and dose-dependently increased the firing rate, spikes/burst, and burst firing of VTA neurons. Ethanol (250-1000 mg/kg/i.v.) administration produced similar increments in electrophysiological parameters. In addition, a second group of rats was pretreated with the alcohol-dehydrogenase inhibitor 4-methylpyrazole (90 mg/kg) intraperitoneally (i.p.), and ethanol and acetaldehyde were administered i.v. at the same doses, 48 h later. In this group, ethanol effects were drastically reduced and the firing rate, spikes/burst, and burst firing were not significantly altered. In contrast, acetaldehyde fully retained its capacity to stimulate electrophysiological indices. The results indicate that acetaldehyde produces electrophysiological actions on VTA neurons in vivo, similar to those produced by ethanol, and significantly participate in ethanol-induced increment in DA neuronal activity. These results also suggest that acetaldehyde, by increasing DA neuronal activity in the VTA, may significantly contribute to the centrally mediated positive motivational properties of ethanol, which would oppose the well-known peripherally originating aversive properties.

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“…Although it is possible to overcome the type II error that may plague individual studies, meta-analysis cannot correct biases or suboptimal design strategies in the original reports: for example, the inclusion of undetected alcoholics who might have depressed gastric ADH levels, 34 the effect of including study subjects of different ethnic backgrounds who may have genetically different abilities to metabolize equivalent amounts of alcohol, 40 or women who may have lower levels of gastric ADH. 35 Finally, it is important to recognize that presumably healthy subjects were the participants in the studies pooled for analysis.…”

Section: Discussionmentioning

confidence: 99%

Effect of histamine-2 receptor antagonists on blood alcohol levels

Weinberg

Burnham²,

Berlin

1998

J Gen Intern Med

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OBJECTIVE:To determine the effect, if any, of histamine type 2 receptor antagonists (H 2 RAs) on serum alcohol levels under various conditions including type of H 2 RA receptor antagonist, alcohol dose, and fed status of the subject. STUDY DESIGN:Meta-analysis of the published literature.DATA SOURCES: Studies were identified by MEDLINE (January 1982 through December 1997) using the key words H 2 receptor antagonists and alcohol. Other studies were identified by reviewing bibliographies of retrieved articles and by discussion with colleagues. STUDY SELECTION:Studies were selected if they involved the coadministration of H 2 RAs and alcohol in healthy, human volunteers. Studies that may have addressed this goal but were performed in another context, for instance the measurement of ulcer healing, were excluded. DATA EXTRACTION:Data were extracted on the design, number of participants, participant characteristics, type and dose of H 2 RA administered, serum alcohol levels (measured as C max ) along with standard deviations, dose of alcohol received, and fed or fasted status of participants. Alcohol dose was arbitrarily divided into low dose ( Յ 0.5 g/kg body weight) versus high dose ( Ͼ 0.5 g/kg body weight). In addition, studies involving ranitidine and cimetidine were stratified by sample size into small ( n Յ 10) versus not small ( n Ͼ 10). MEASUREMENTS AND MAIN RESULTS:

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Lack of alcohol dehydrogenase isoenzyme activities in the stomach of Japanese subjects

Cited by 91 publications

References 11 publications

<i>Helicobacter pylori</i> Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man

<i>Helicobacter pylori</i> Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

Effect of histamine-2 receptor antagonists on blood alcohol levels

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