Gastric Alcohol Dehydrogenase Activity Research Articles

The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection.

IntroductionHelicobacter pylori infection is associated with decreased alcohol dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH activity depends on the severity of inflammation and mucosal injury. This damage can be a reason of the release of enzyme from gastric mucosa and leads to the increase of the ADH activity in the sera of patients with H. pylori infection.Material and methodsSerum samples were taken from 140 patients with H. pylori infection. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.ResultsThe activity of ADH IV in the serum of patients with H. pylori infection increased about 42% (7.86 mU/l) in the comparison to the control level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682 mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%, positive and negative predictive values were 91% and 84% respectively. Area under ROC curve for ADH IV was 0.84.ConclusionsHelicobacter pylori infection of gastric mucosa is reflected in the serum by significant increase of class IV and total ADH activity. The results suggest a potential role for ADH IV as a marker of H. pylori infection.

Alcohol Dehydrogenase (ADH) Isoenzyme Activity in the Sera of Patients with Helicobacter pylori Infection

Human gastric mucosa contains three classes of alcohol dehydrogenase (ADH) isoenzymes: I, III, and IV. Various factors have been found to influence gastric ADH activity. One of them is Helicobacter pylori infection, which is associated with gastric mucosal injury and leads to a decrease in gastric ADH activity. The aim of the study was to assess the effect of H. pylori infection on the serum activity of ADH isoenzymes. Serum samples were taken from 35 patients with H. pylori infection and from 35 healthy subjects. For measurement of class I isoenzyme activity we employed the fluorometric method, with class-specific fluorogenic substrate (4-methoxy-1-naphthaldehyde). The activities of class III and IV ADH isoenzymes were measured by the photometric method with formaldehyde and with m-nitrobenzaldehyde as substrate, respectively. Total activity of ADH was measured by a photometric method with p-nitrosodimethylaniline. The total activities of ADH and class IV isoenzyme were significantly higher in sera of patients with H. pylori infection compared to healthy subjects. The serum activity of other tested isoenzymes of ADH did not differ significantly between infected and noninfected groups. We conclude that H. pylori infection of gastric mucosa is reflected in the serum by a significant increase in class IV and total ADH activity.

The effects of pregnancy on ethanol clearance

We have studied the effects of pregnancy on ethanol clearance rates and on blood and urine ethanol concentrations (BECs and UECs) in adult Sprague–Dawley rats infused with ethanol intragastrically. Pregnant rats had greater ethanol clearance following an intragastric or intravenous ethanol bolus (3 or 0.75 g/kg, respectively) relative to non-pregnant rats ( p < 0.05). Pregnant rats infused with ethanol-containing diets for several days had lower ( p < 0.05) UECs than non-pregnant rats when given the same dose of ethanol. Non-pregnant rats infused ethanol-containing diets at two levels of calories (the higher caloric intake required by pregnant rats [220 kca/kg 75/d] or the normal calories required for non-pregnant rats [187 kcal/kg 75/d]) had statistically equal UECs, suggesting that increased caloric intake was not responsible for the effect of pregnancy. While the activity of hepatic alcohol dehydrogenase (ADH) did not differ with pregnancy, gastric ADH activity was increased ( p < 0.001). Furthermore, total hepatic aldehyde dehydrogenase (ALDH) and hepatic mitrochrondrial protein were increased ( p < 0.05) and hepatic CYP2E1 activity was suppressed ( p < 0.05). The results suggest that pregnancy increases ethanol elimination in pregnant rats by: 1) induction of gastric ADH; 2) elevated hepatic ALDH activity; and 3) increased mitochondrial respiration. The greater ethanol clearance results in lower tissue ethanol concentrations achieved during pregnancy for a given dose, and this may have clinical significance as a mechanism to protect the growing fetus from ethanol toxicity.

Gastric alcohol dehydrogenase activity in man: influence of gender, age, alcohol consumption and smoking in a caucasian population.

The stomach is involved in first-pass metabolism of alcohol in humans. As conflicting data were published regarding the influence of age and gender on the activity of alcohol dehydrogenase (ADH) in human gastric mucosa, the present study aimed at the investigation of these and other potentially confounding factors (alcohol consumption, smoking, drug intake) on its activity in a Caucasian population. ADH activity was assessed in endoscopic gastric biopsy specimens from 111 Caucasian subjects aged 20-80 years, of whom 51 were females. Highest ADH activity was measured at ethanol concentrations between 150 and 500 mM. Mean ADH activity was higher in antral specimens than in those from the gastric corpus of the same subjects. ADH activity decreased with increasing age in males, while the values in females aged 41-60 years were higher than those in women aged 20-40 or 61-80 years. In men aged 20-40 years, consumption of larger quantities of alcohol (>0.8 g/kg body weight/day) was associated with reduced ADH activity. H(2)-Receptor antagonist treatment also decreased gastric ADH activity. The results indicate that ADH activity in human gastric mucosa is negatively associated with consumption of larger quantities of alcohol. The question of whether ADH activity is higher in males or females can only be answered with respect to age. The gastric ADH activity in young men is distinctly higher compared to young women, but the opposite holds true in middle-aged subjects.

Effect of Helicobacter pylori Infection on the Activity of Class I, III and IV Alcohol Dehydrogenase in the Human Stomach

Background/Aims: In the human stomach various alcohol dehydrogenase (ADH) isoenzymes exist. The gastric ADH activity is affected by a number of factors including also the infection of Helicobacterpylori. The objective was to investigate the activity of alcohol dehydrogenaseisoenzymes of class I, III and IV in endoscopic specimens of gastric mucosa from the different parts of the stomach of men and women, considering the H. pylori infection. Method: Biopsy samples of gastric mucosa were taken from the corpus and antrum of 68 patients (42 of men and 26 of women) suspected for gastric ulcer. The colonization of H. pylori was present in 22 samples of men and 13 samples of women. The activity of class I isoenzyme was measured by the fluorimetric method with a specific substrate (4-methoxy-1-naphthaldehyde) and the activity of class III and IV by the photometric method with n-octanol and m-nitrobenzaldehyde as a substrates, respectively. Results: In infected samples from the antrum and corpus of men’s and women’s stomachs the activity of class IV isoenzyme was decreased as compared to non-infected specimens. The activity of class III isoenzyme was decreased in the infected samples from the corpus of male patients, but the activity of class I does not significantly differ between infected and noninfected specimens from both sexes. Conclusion:H. pylori infection leads to significant decrease in the activity of class IV ADH in the stomach of men and women.

Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity

Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied. A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n = 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later. No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n = 39) and those 50 years or younger (n = 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus. H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.

Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity

Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity

Effect of thyroid hormone on the alcohol dehydrogenase activities in rat tissues.

The effects of thyroid hormone on hepatic and gastric alcohol dehydrogenase (ADH) activities (nM of NADH/min/mg of cytosolic protein) have been investigated in male Sprague Dawley rats treated with thyroxine (1 mg/kg, po) for 14 days. Whereas hepatic ADH activity in thyroxine-treated rats decreased by 61.3% of control rats (26.4 vs 43.2, p<0.001), gastric ADH activity increased by 262.9% of control rats (4.9 vs 1.9, p<0.001). As for the activities of the lung and kidney, thyroxine treatment did not produce any statistically significant changes. These data suggest that thyrotoxicosis causes a decrease of hepatic alcohol metabolism, and that the increase of gastric ADH activity in thyrotoxic rats can partly restore the first-pass metabolism of ethanol.

Contribution of Gastric Oxidation to Ethanol First Pass Metabolism in Baboons

A portion of ingested alcohol does not reach the systemic blood, undergoing a first-pass metabolism (FPM) during gastric and hepatic circulation. To determine whether the stomach can metabolize sufficient ethanol to account for the FPM, and to what extent gastric alcohol dehydrogenase (ADH) activity is responsible, the hepatic vein, the portal vein, and the aorta were cannulated nonocclusively in baboons to measure the conversion of ethanol to acetate in vivo. 14C-ethanol (300 mg/kg as a 15% solution) was given intragastrically (IG) whereas 3H-acetate was continuously infused intravenously (IV). 14C-acetate was measured after exhaustive evaporation of ethanol. Simultaneous sampling of hepatic venous, portal and arterial blood was carried out for 3 hr, at the end of which the same alcohol dose was given IV to calculate the Michaelis-Menten parameters of elimination. Analysis of the IV and IG ethanol curves revealed a FPM of 94+/-11 mg/kg (31% of dose). The portal-arterial differences were negative for 3H-acetate (indicating net extraction) and positive for 14C-ethanol and 14C-acetate (indicating net output). Portal acetate production (extraction plus net output multiplied by the portal plasma flow) increased with time and accounted, over the first 3 hr (82+/-13 mg/kg), for 87% of the FPM. Alcohol oxidation by gastric ADH activity (28.7+/-7.2 mg/kg) accounted for only 31% of the FPM. The in vivo oxidation of ethanol to acetate in the upper digestive tract accounts for the FPM of ethanol and is mediated, at least in part, by ADH activity.

Effects of Helicobacter pylori infection and gastric pathology on gastric alcohol dehydrogenase activity

Effects of Helicobacter pylori infection and gastric pathology on gastric alcohol dehydrogenase activity

How does Helicobacter pylori infection affect gastric alcohol dehydrogenase activity in patients with gastritis

BACKGROUND: Angiogenesis is a complex process that provides tumoral cells with and adequate growth environment and plays a role in metastasis. Several studies have demonstrated the expression of some angiogenic factors, such as platelet-derived endothelial cell growth factor (PD-ECGF) and vascular growth factor (VEGF) in sub-sets of gastric carcinomas. Helicobacter pylori (H pylori) has been considered to be a risk factor for gastric cancer development. Whether H pylori infection influences the expression of PD-ECGF and VEGF in gastric epithelial cells has never been studied. AIM: to assess whether H pylori may affect the cellular pathways that lead to expression of angiogenic factors by gastric cancer cells. METHODS: The gastric cancer cell lines SNU 668, KATOIII, SNU 16 and SNU 638 were tested. The cells were co-cultured with H pylori (ATCC 43504) for 24 hours. Equal amounts(lO ug) of protein extracts were separated by SDS-PAGE and western blots were performed with PD-ECGF, VEGF and control actinspecific antibodies. Protein extracts from control cells cultured in the absence of H pylori were run in parallel. RESULTS: Expression of VEGF was detected in the four cancer cell lines while PD-ECGF protein was only detected in SNU 668 and SNU 638 cells. Co-culture with H pylori resulted in decreased protein levels of both PD-ECGF and VEGF factor. However, while the levels of VEGF decreased in the four cell lines tested, a drop in PD-ECGF levels was only detected in SNU 638 cells. In contrast. the levels of actin were similar in cells with or without exposure to H pylori. CONCLUSIONS: The angiogenic factors PD-ECGF and VEGF are expressed in various gastric cancer cell lines. The interaction of intact H pylori organisms with gastric cancer cells causes a reduction in VEGF and PD-ECGF protein levels. These findings provide additional evidence that H pylonbacterial products may affect gastric cell pathways in a direct manner, in the absence of inflammatory products. The biological implications of these effects in vivo may be of relevance to the understanding of H pylori-related gastric carcinogenesis. 5654

Sex-dependent induction of alcohol dehydrogenase activity in rats

The glycolethers 2-methoxyethanol (2-ME), 2-ethoxyethanol (2-EE), and 2-butoxyethanol are widely used organic solvents with teratogenic, spermatotoxic, and hematotoxic effects due to the respective alkoxyacetic acid metabolites formed via alcohol dehydrogenase (ADH). ADH displays sexually dimorphic activities in adult rats, and is probably at least in part under the control of testosterone. The aim of this study was to investigate whether induction of ADH is also sex-dependent. Ethanol, 2-ME, and 2-EE were tested as inducers of hepatic and gastric ADH in female, male, and castrated male rats. The activity of hepatic ADH was higher in female than in male rats, while the activity of gastric ADH was higher in male than in female rats. The activities of ADH increased with increasing chain length of the glycolethers and alcohols. Castration of male rats led to a female pattern of ADH activity, i.e. increased activity of hepatic ADH and decreased activity of gastric ADH. Ethanol had no inducing effect on hepatic ADH in either male or female rats. 2-ME and 2-EE caused an increase in the activity of hepatic ADH in male and castrated male rats only. The present data demonstrate a different expression of ADH isoenzymes in male and female rats, and a sex-dependent induction of ADH isoenzymes. The different possible regulatory mechanisms for the different ADH isoenzymes require further investigation.

Nitric oxide-mediated regulation of gastric H+, K+ -ATPase and alcohol dehydrogenase following ethanol-induced injury in rats.

The mucosal protective effect of nitric oxide (NO) was examined by using N(G)-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor and nitroprusside (NP) as NO donating agent, in ethanol-induced rat gastric lesion model. The results are summarized as follows: (1) As gastric tissue samples were examined by light microscopy, intragastric exposure of ethanol was demonstrated to induce gastric injury, which was more prominent in female rats. The depletion of NO by L-NAME treatment exacerbated the ethanol-induced gastric lesion but NP together with ethanol promoted repair of the mucosal injury, especially in female rats. (2) Gastric H+, K+ -ATPase enzyme activity, which was responsible for acid secretion, seemed not to be effected by ethanol treatment. Together with ethanol, L-NAME treatment activated, whereas NP treatment inhibited, the enzyme activity in female rats. (3) Ethanol treatment inhibited gastric alcohol dehydrogenase (ADH) activity, which was responsible for the first-pass metabolism of ethanol. Together with ethanol, L-NAME did not effect the enzyme activity whereas NP treatment disappeared the inhibitory effect of ethanol in both gender. Hydroxyl radical (OH*) scavenger activity was found to increase in ethanol and ethanol + NP groups in both sexes, but superoxide radical (O2-*) scavenger activity did not change. The results indicate that NO may ameliorate the damaging effect of ethanol possibly by regulating acid secretion, ethanol metabolism, and antioxidant content in rat gastric mucosa.

First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying

Background—Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed...

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

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.

Helicobacter pylori eradication increases gastric alcohol dehydrogenase activity but does not affect ethanol first pass metabolism

Helicobacter pylori eradication increases gastric alcohol dehydrogenase activity but does not affect ethanol first pass metabolism

Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First‐Pass Metabolism of Ethanol in Alcohol‐Fed Rats

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 +/- 0.25 vs. 2.43 +/- 0.20 mM x hr, p < 0.05) and gastric ADH activity (184 +/- 7 vs. 335 +/- 41 micromol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 +/- 31 vs. 184 +/- 7 micromol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 +/- 0.07 vs. 1.71 +/- 0.24 mM x hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.

Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

The role of gastrointestinal factors in alcohol metabolism.

Although the liver is the major organ responsible for ethanol metabolism, such metabolism also occurs in the gastrointestinal (GI) tract. However, compared to the liver, GI metabolism of ethanol is quantitatively much lower. Various enzyme systems have been characterized in GI mucosal cells including various isozymes of alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP 2E1) and catalase. Gastric ADH activity is one factor by which first pass metabolism (FPM) is influenced and its activity is modulated by genetics, gender, age, drugs and gastric morphology. Another important factor in FPM of ethanol is the speed of gastric emptying. In addition to mucosal ethanol metabolism, ethanol can also be oxidized by many bacterial species in the upper GI tract including oropharynx and stomach as well as in the large intestine. GI metabolism of ethanol may influence systemic bioavailability of ethanol and may lead to local toxicity most likely mediated by acetaldehyde. Such toxicity could be of importance in ethanol-associated carcinogenesis.

Effects of Cimetidine on Blood Ethanol Levels after Alcohol Ingestion and Genetic Polymorphisms of σ‐Alcohol Dehydrogenase in Japanese

Administration of cimetidine, an H2-receptor antagonist increases blood alcohol concentrations. This has been attributed to decreased gastric first-pass metabolism of ethanol caused by cimetidine's inhibitory effect on gastric alcohol dehydrogenase (sigma-ADH) activity. Molecular studies on sigma-ADH showed that a point mutation might occur at position 287 (G --> T) of the sigma-ADH gene in Japanese deficient type of sigma-ADH activity. To clarify the relationship between first-pass metabolism of ethanol and polymorphism of sigma-ADH, we analyzed the nucleotide sequence at positions 287 and 294 of sigma-ADH in 11 individuals who were administered ethanol orally before and after treatment with cimetidine. Higher blood ethanol levels after cimetidine administration were found in 4 of 11 cases (group A), whereas high blood ethanol levels were observed in 7 of 11 cases (B group), irrespective of cimetidine administration. Genetic polymorphisms at position 287 and 294 were not observed in all subjects. Even in 59 Japanese men with various alcoholic liver diseases, no polymorphisms at position 287 were observed by restriction-length polymorphisms with Avail digestion after polymerase chain reaction.