Gender‐related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans

Chrostek, Lech; Jelski, Wojciech; Szmitkowski, Maciej; Puchałski, Z

doi:10.1002/jcla.10076

Cited by 78 publications

(62 citation statements)

References 22 publications

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“…Heavy alcohol consumption enhances the probability of both atrial and lifethreatening ventricular arrhythmias and atrioventricular block through the destabilization of potassium and magnesium metabolism and the stimulation of catecholamine. 28,29 Further, women have lower alcohol dehydrogenase activity in the liver than men, 30 so that women have higher blood alcohol concentrations than men after ingestion of the same dose of alcohol, even when the dose is adjusted for body weight. 31 The Nurse's Health study 19 did not find the excess mortality, but the number of deaths among heavy drinkers of Ն30g ethanol per day in that cohort was also small (nϭ9).…”

Section: Discussionmentioning

confidence: 99%

Alcohol Consumption and Mortality From Stroke and Coronary Heart Disease Among Japanese Men and Women

Ikehara

Iso

Toyoshima

et al. 2008

Stroke

114

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Background and Purpose-Previous studies have demonstrated the association between alcohol consumption and cardiovascular mortality. However, the sex-specific association between alcohol consumption and mortality from stroke and coronary heart disease remains unclear. Methods-Between 1988 and 1990, 34 776 men and 48 906 women aged 40 to 79 years completed a self-administered questionnaire including information about alcohol consumption. They were followed-up for a median duration of 14.2 years. Results-Of the 83 682 respondents, 1628 died from stroke and 736 died from coronary heart disease. For men, heavy drinking (Ն46.0 g ethanol/day) was associated with increased mortality from total, hemorrhagic, and ischemic strokes, whereas light-to-moderate drinking was associated with reduced mortality from total cardiovascular disease, compared with not drinking. The respective multivariable hazard ratios (95% CI) were 1.48 (1.22 to 1.80) for total stoke, 1.67 (1.17 to 2.38) for hemorrhagic stroke, 1.35 (1.04 to 1.75) for ischemic stroke, and 0.88 (0.78 to 1.00) for total cardiovascular disease. Women who were heavy drinkers (Ն46.0 g ethanol/day) showed increased mortality from coronary heart disease, and there was reduced mortality from total cardiovascular disease for drinkers of 0.1 to 22.9 g ethanol per day compared with mortality for nondrinkers. The respective multivariable hazard ratios (95% CI) for the 2 categories of drinkers were 4.10 (1.63 to 10.3) and 0.75 (0.62 to 0.91). Conclusions-Heavy alcohol consumption is associated with increased mortality from total stroke, particularly hemorrhagic stroke, and total cardiovascular disease for men, and from coronary heart disease for women, whereas light-to-moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes.

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Section: Discussionmentioning

confidence: 99%

Alcohol Consumption and Mortality From Stroke and Coronary Heart Disease Among Japanese Men and Women

Ikehara

Iso

Toyoshima

et al. 2008

Stroke

114

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“…We Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with colorectal cancer hypothesised that the changed activities of these enzymes in cancer cells were reflected in the serum and perhaps could thus be helpful for diagnosing colorectal cancer. But it is necessary to remember that isoenzymes of ADH and ALDH are present in large quantities in the liver, and also occur in the different organs such as gastrointestinal tract, lungs, kidneys and breast [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with colorectal cancer

et al. 2007

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Various isoenzymes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exist in human colorectal mucosa. In our last experiments we have shown that ADH and ALDH are present also in colorectal cancer cells. Moreover the activities of total ADH and class I isoenzymes were significantly higher in cancer tissue than healthy mucosa. This may suggest that these changes may be reflected by enzyme activity in the serum. Therefore, we have measured the activity of total ADH, and classes I-IV of this enzyme and ALDH in the sera of patients suffering from this cancer. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. Serum samples were taken for routine biochemical investigations from 52 patients with colorectal carcinoma before treatment. A statistically significant increase of class I ADH isoenzymes was found. Therefore the total ADH activity was also significantly increased. The total ALDH and the activity of other tested ADH isoenzymes were unchanged. We also observed the increasing tendency of ADH I activity in accordance with the advance of disease. The activity of class I ADH isoenzymes was elevated in the serum of patients with colorectal cancer. This activity was derived from colorectal cancer cells and probably from severely damaged liver by metastatic disease.

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“…Pharmacokinetic studies revealed that women have lower levels of gastric and hepatic ADH, resulting in increased blood alcohol levels and EtOH toxicity (Frezza et al, 1990;Chrostek et al, 2003). However, Maly and Sasse (1991) found that hepatic ADH activity is enhanced in women.…”

Section: Introductionmentioning

confidence: 99%

“…However, Maly and Sasse (1991) found that hepatic ADH activity is enhanced in women. Although only minor variations in ALDH activity between men and women have been reported, ALDH activity is higher in male hamsters than in females (Maly and Sasse, 1991;Lee et al, 2001;Chrostek et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pregnane X Receptor–Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity

Spruiell

Gyamfi

Yeyeodu

et al. 2015

J Pharmacol Exp Ther

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Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXRhumanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor a, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females.

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Gender‐related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans

Cited by 78 publications

References 22 publications

Alcohol Consumption and Mortality From Stroke and Coronary Heart Disease Among Japanese Men and Women

Alcohol Consumption and Mortality From Stroke and Coronary Heart Disease Among Japanese Men and Women

Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with colorectal cancer

Pregnane X Receptor–Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity

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