Chronic alpha-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism.

Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired alpha-tocopherol status. Potentially, this implies a therapeutic role for alpha-tocopherol, especially as we have shown that supplemental alpha-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J.

Inhibition of alcohol-associated colonic hyperregeneration by alpha-tocopherol in the rat.

Background: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption.

Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo.

Alcohol can be considered as a nutritional toxin when ingested in excess amounts and leads to skeletal muscle myopathy. We hypothesized that altered protease activities contribute to this phenomenon, and that differential effects on protease activities may occur when: (1) rats at different stages in their development are administered alcohol in vivo; (2) acute ethanol treatment is superimposed on chronic alcohol-feeding in vivo; and (3) muscles are exposed to alcohol and acetaldehyde in vivo and in vitro. In acute studies, rats weighing approximately 0.

Serum collagen type VI and XIV and hyaluronic acid as early indicators for altered connective tissue turnover in alcoholic liver disease.

Hepatic fibrosis in alcoholic liver disease often heralds progression to cirrhosis and, therefore, noninvasive parameters are required for early diagnosis and follow-up. Collagens VI and XIV, procollagen-III-N-propeptide, hyaluronic acid, and active transforming growth factor-beta1 (TGF-beta1) were measured in healthy volunteers, patients with alcoholic cirrhosis, and heavy drinkers without cirrhosis. Noncirrhotic alcoholics were assigned to two groups with either normal aspartate aminotransferase or levels > or = 2 normal.

Increased rectal cell proliferation following alcohol abuse.

Background: Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers.

Methods: Rectal biopsies were taken from 44 heavy drinkers and 26 controls.

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 of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol.

Cell proliferation and its evaluation in the colorectal mucosa: effect of ethanol.

Colorectal cell turn over is affected by numerous factors including diets, alcohol consumption, smoking or age and is also significantly changed in certain mucosal diseases including benign and malignant tumors. Mucosal hyperregeneration is associated with an increased cancer risk since it increases the susceptibility of the mucosa towards the action of carcinogens. The measurement of colorectal mucosal regenerativity can be used for risk assessment in carcinogenesis.

Alcohol and cancer.

A great number of epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx, and the esophagus, and for the liver. In contrast to those organs, the risk by which alcohol consumption increases cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol.

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.

Alcohol dehydrogenase in the human colon and rectum.

Alcohol dehydrogenase (ADH) activities were measured in rectal biopsies from 55 patients (28 males, 27 females aged 22-81 years), in colonic biopsies from 19 patients (10 males, 9 females aged 21-81 years) and in three surgical specimens. All patients had normal mucosa as determined by light microscopy. The activity of rectal ADH was comparable to gastric ADH activity and did not exhibit any significant gender effect (5.

[Carbohydrate-deficient transferrin. A new, highly specific marker for chronic alcohol consumption].

To test the value of carbohydrate-deficient transferrin (CDT) as a marker for chronic alcohol consumption, its concentration was measured in the serum of 74 patients (48 men, 26 women; mean age 48 [18-71] years) with various alcohol-related liver diseases, ten patients (six men, four women; mean age 61 [24-90] years) with non-alcohol related liver diseases and 30 healthy controls (12 men, 18 women; mean age 37 [19-84] years). In the healthy women the mean CDT concentration was 19.7 +/- 6.

Effect of alcohol on gastrointestinal cell regeneration as a possible mechanism in alcohol-associated carcinogenesis.

Chronic ethanol consumption is a major risk factor for oropharyngeal, esophageal, and rectal cancer. Because hyperregenerative gastrointestinal mucosa has an increased susceptibility towards chemical carcinogens and thus influences carcinogenesis, various studies have been performed to evaluate the effect of chronic ethanol consumption on mucosal cell turnover. In the rat, morphometric analysis showed that in chronically ethanol-fed rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue, and the base of the tongue were significantly enlarged.

Increased messenger RNA levels for low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver after long-term ethanol ingestion.

Because long-term alcohol intake leads to severe alterations of cholesterol metabolism resulting in both elevated serum cholesterol levels and increased hepatic concentrations of cholesterol esters, we investigated the effect of long-term ethanol consumption on the hepatic messenger RNA (mRNA) content of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein receptor, two major regulatory factors in cholesterol metabolism, and of apoprotein E. Twenty-four male Sprague-Dawley rats were pair-fed nutritionally adequate liquid diets containing 36% of total calories as either ethanol or isocaloric carbohydrates for 3 wk. In addition, the lipid content of the diets was varied, resulting in 35%, 17.

Enhancement of ethanol induced rectal mucosal hyper regeneration with age in F344 rats.

Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. In this study the combined effect of these two factors on colorectal cell regeneration has been investigated. Ninety male F344 rats aged 2, 12, and 22 months were pair fed nutritionally adequate liquid diets containing 36% of total energy either as ethanol or isoenergetic carbohydrates.

Ethanol metabolism in the gastrointestinal tract and its possible consequences.

Ethanol is oxidised not only in the liver, but also in the gastrointestinal tract. Although this ethanol metabolism is less than that of the liver, it has some important relevance with respect to the first pass metabolism of alcohol and to ethanol induced tissue toxicity. In the gastrointestinal tract, ethanol can be metabolised not only in the mucosal cell via alcohol dehydrogenase (ADH) and microsomal ethanol oxidising system (MEOS), but also in a great variety of bacteria.

Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol.

Epidemiology and pathophysiology of ethanol-associated gastrointestinal cancer.

Various epidemiological studies have given evidence on the correlation between alcohol intake and different types of cancer, especially in the upper alimentary and respiratory tract and in the liver. This review discusses the tumour stimulating effects of ethanol associated mechanisms.

Effect of age and gender on in vivo ethanol elimination, hepatic alcohol dehydrogenase activity, and NAD+ availability in F344 rats.

It has been reported that aging strikingly decreases in vivo ethanol metabolism in F344 rats without major effects on hepatic alcohol dehydrogenase (ADH) activity. Because hepatic ADH activity is not always rate limiting in the oxidation of ethanol, we measured in vivo ethanol elimination rate (EER), hepatic ADH activity, and the hepatic-cytoplasmic and mitochondrial redox states after acute ethanol application in 2- and 12-month-old F344 rats of both sexes. In male, but not in female, animals EER decreased with age significantly, by 28% (P less than 0.

Human gastric alcohol dehydrogenase: in vitro characteristics and effect of cimetidine.

The presence of at least two types of alcohol dehydrogenase has been demonstrated in surgical specimens from the human stomach. One isoenzyme has a Km of approximately 1-2 mM for ethanol comparable to that of class I alcohol dehydrogenase isoenzyme as defined for the liver. This isoenzyme can also be detected by immunohistology using a polyclonal rabbit antibody against human liver class I alcohol dehydrogenase.

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.