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Biomedical subjects

C S Lieber

Publications and source records attributed to C S Lieber.

At least 109 records · Page 6Linked to original sources
PubMed1994

Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases.

Alcoholic and, to a lesser extent, nonalcoholic patients with liver disease have serum antibodies to acetaldehyde-protein adducts produced in vitro. These antibodies presumably reflect the presence of adducts in the liver, but the protein that triggers this immune response has not been identified. To study this, we measured the reactivity of cytosolic proteins to rabbit IgG developed against a P-450 2E1-acetaldehyde adduct, isolated from alcohol-fed rats, that recognizes acetaldehyde-modified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody-linked alkaline phosphatase activity in 4 normal livers and in needle biopsy specimens from subjects with liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, except for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen-acetaldehyde adduct we reported to be markedly increased in rats with experimentally induced cirrhosis. The immunostaining intensity in the alcoholic patients with liver disease was eightfold (p < 0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p < 0.02) than the weak staining in normal livers; it correlated with the degree of inflammation and serum AST or gamma-glutamyl transpeptidase activities. The adduct was reproduced on incubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, whereas higher concentrations yielded many additional adducts; the adduct also reacted with IgG antibody to rat collagen type I and disappeared after digestion with collagenase, suggesting that the target protein is a form of collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1994

Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon.

BACKGROUND/AIMS: Polyunsaturated soybean lecithin (55%-60% phosphatidylcholine [PC]) protects against fibrosis in alcohol-fed baboons. The present study was undertaken to determine whether PC is the active agent. METHODS: Virtually pure PC (equivalent to that contained in the lecithin) was administered for up to 6.5 years with or without alcohol, and the results were compared with those of unsupplemented groups. RESULTS: Control livers remained normal, whereas 10 of 12 baboons fed alcohol without PC developed septal fibrosis or cirrhosis with transformation of 81% +/- 3% of the hepatic lipocytes to collagen-producing transitional cells. By contrast, none of the eight animals fed alcohol with PC developed septal fibrosis or cirrhosis, and only 48% +/- 9% of their lipocytes were transformed, indicating that PC was indeed the protective compound. Ethanol feeding also resulted in decreased liver phospholipids and PC, and both were corrected by the supplementation. Furthermore, PC stimulated collagenase activity in cultured lipocytes. This PC consisted of several species, mainly dilinoleoylphosphatidylcholine (40%-52%) and palmitoyl-linoleoylphosphatidylcholine (23%-24%). Only dilinoleoylphosphatidylcholine duplicated the effect of the PC on collagenase. Other species of PC, phosphatidylethanolamine, free fatty acids, or choline were without effect. CONCLUSIONS: PC prevents alcohol-induced fibrosis and cirrhosis in nonhuman primates, and dilinoleoylphosphatidylcholine appears to be the active species, possibly by promoting collagen breakdown.

Animals↗
PubMed1994

Interactions between alcohol and beta-carotene in patients with alcoholic liver disease.

We found lower plasma beta-carotene concentrations in alcoholics than in control subjects, but heavy drinkers (> or = 200 g/d) had about twice the beta-carotene of those drinking less (P < 0.01), with a significant correlation between plasma beta-carotene and alcohol intake (r = 0.6, P < 0.001). When beta-carotene beadlets (30-60 mg/d) were administered to hospitalized alcoholics given controlled diets, those with cirrhosis had a much lower plasma beta-carotene response than those without; the latter in turn responded with lower beta-carotene concentrations than did control subjects. Plasma retinol, alpha-tocopherol, and other carotenoids, such as lycopene, did not differ significantly. We concluded that plasma beta-carotene is relatively increased by heavy alcohol consumption, whereas in patients with liver damage, especially cirrhosis, it is lowered. In these patients, beta-carotene supplementation may be justified, but this should be coupled with control of drinking because of possible hepatotoxic alcohol-beta-carotene interactions.

Adult↗
PubMed1994

Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine.

UNLABELLED: Phosphatidylethanolamine N-methyltransferase participates in the synthesis of membrane phosphatidylcholine. Its activity was reported to be decreased in patients with alcoholic cirrhosis, but it is not known whether this is a consequence of the cirrhosis or precedes it. This question was studied in a baboon model of alcohol-induced fibrosis. Phosphatidylethanolamine N-methyltransferase activity was measured in sequential percutaneous needle liver biopsies by the conversion of phosphatidylethanolamine to phosphatidylcholine, using radioactive S-adenosylmethionine as a methyl donor. Chronic alcohol consumption (1-6 years) significantly decreased hepatic phospholipid and phosphatidylcholine levels and reduced phosphatidyl-ethanolamine N-methyltransferase activity even before the development of fibrosis. These effects were prevented or attenuated by supplementing the diet with 2.8 g/1000 kcal of a preparation rich in dilinoleoyl phosphatidylcholine, a highly bioavailable phosphatidylcholine species. There were significant (p < 0.001) correlations between phosphatidylethanolamine N-methyltransferase activity and both hepatic phosphatidylcholine (r = 0.678) and total phospholipid (r = 0.662). CONCLUSIONS: 1. Alcohol consumption diminishes phosphatidylethanolamine N-methyltransferase activity prior to the development of cirrhosis and decreases the hepatic content of its product, namely phosphatidylcholine, a key component of cell membranes. This may promote hepatic injury and possibly trigger fibrosis. 2. Phosphatidylcholine administration ameliorates the ethanol-induced decrease in phosphatidylethanolamine N-methyltransferase activity and corrects phospholipid and phosphatidylcholine depletions, thereby possibly contributing to the protection against alcoholic liver injury.

Animals↗
PubMed1994

Hepatic and metabolic effects of ethanol: pathogenesis and prevention.

Mechanisms of the hepatotoxicity of ethanol are reviewed, including effects resulting from alcohol dehydrogenase (ADH) mediated excessive hepatic generation of NADH and acetaldehyde. Gastric ADH explains first-pass metabolism by ethanol; its activity is low in alcoholics and in females and is decreased by some commonly used drugs. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last 25 years have culiminated in the molecular elucidation of the ethanol-inducible cytochrome P-450 (2E1) which causes metabolic tolerance to ethanol and to various commonly used medications, enhanced degradation of testosterone and vitamin A (with vitamin A depletion) and selective hepatic perivenular toxicity. The latter results from free radical generation and activation of various xenobiotics, causing increased vulnerability of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens and even nutritional factors such as vitamin A and beta-carotene. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation which promotes GSH depletion and lipid peroxidation and other toxic effects. Nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other 'supernutrients' include polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human primates.

Acetaldehyde↗
PubMed1994

Mechanisms of ethanol-drug-nutrition interactions.

Mechanisms of the toxicologic manifestations of ethanol abuse are reviewed. Hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive hepatic generation of nicotinamide adenine dinucleotide and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) pathway, the microsomal ethanol-oxidizing system, which involves a specific cytochrome P450. It generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications and carcinogens. The contribution of gastric alcohol dehydrogenase to the first pass metabolism of ethanol and alcohol-drug interactions is now recognized. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and beta-carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other supernutrients include polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human primates. Thus, a better understanding of the pathology induced by ethanol has now generated improved prospects for therapy.

Acetaldehyde↗
PubMed1994

Diagnostic utility of laboratory tests in alcoholic liver disease.

Alcoholic liver disease is an important health problem in the US. A public health approach is proposed, using laboratory tests to identify patients with early fibrosis of the liver. A variety of serological markers of liver fibrosis based on collagen-related products (e.g., amino-terminal propeptides of type III procollagen) have been investigated. Further studies are needed to determine the optimal combination of tests for discriminating between steatosis and early fibrosis. Laboratory tests are also useful in excluding nonalcoholic liver diseases such as viral hepatitis, hemochromatosis, and Wilson disease. The monitoring of sobriety in patients with alcoholic liver disease by currently available tests is far from ideal. A new marker of excessive alcohol consumption, carbohydrate-deficient transferrin, is not usually affected by liver disease and thus shows promise as a marker of relapse in alcoholic patients. The development of reliable screening markers of fibrosis and sobriety could potentially reduce the health costs and suffering associated with the complications of alcoholic cirrhosis.

Clinical Laboratory Techniques↗
PubMed1994

Tissue inhibitor of metalloproteinase is increased in the serum of precirrhotic and cirrhotic alcoholic patients and can serve as a marker of fibrosis.

One of the contributory factors to the development of cirrhosis is a decrease in collagenase activity, which may be related to levels of inhibitors such as serum tissue inhibitor of metalloproteinase. We therefore measured serum tissue inhibitor of metalloproteinase and serum procollagen III peptides (another proposed marker of fibrosis) in 16 healthy controls and 44 alcoholic patients with biopsy-proved liver disease, namely steatosis without fibrosis (n = 13), perivenular fibrosis (n = 10), septal fibrosis or cirrhosis or both (n = 15) and alcoholic hepatitis (n = 6). In alcoholic patients, serum tissue inhibitor of metalloproteinase values strongly correlated with fibrosis (rs = 0.70, p < 0.001). Compared with values in controls (177 +/- 12 ng/ml), serum tissue inhibitor of metalloproteinase was significantly elevated in perivenular fibrosis (330 +/- 22 ng/ml, p < 0.05), in septal fibrosis, cirrhosis or both (406 +/- 29 ng/ml, p < 0.001) and in alcoholic hepatitis (526 +/- 140 ng/ml, p < 0.001) but not in steatosis (204 +/- 17 ng/ml). In contrast, procollagen III peptides were significantly increased only in the septal fibrosis-cirrhosis group but not in the perivenular fibrosis group. With the threshold defined as the upper value of the steatosis group (resulting in a specificity of 100%), we found that serum tissue inhibitor of metalloproteinase was elevated in 50% of patients with perivenular fibrosis, in 87% of subjects with extensive fibrosis (septal fibrosis, cirrhosis or both) and in 67% of individuals with alcoholic hepatitis. The overall sensitivity of serum tissue inhibitor of metalloproteinase for detecting either perivenular fibrosis or more extensive fibrosis was 71%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

First pass metabolism of ethanol.

The human stomach has both low and high K(m) ADH isozymes, resulting in significant ethanol metabolism in gastric cells in vitro, and decreased bioavailability of ethanol (first pass metabolism: FPM) in vivo. Intraduodenal or intraportal infusion of amounts of ethanol equivalent to those emptied into the duodenum or disappearing from pylorus-ligated stomachs produced significantly higher blood levels than intragastric administration, whereas portal ligation had no effect, documenting the role of gastric ethanol metabolism in vivo. This "protective barrier" against the systemic effects of ethanol disappears after gastrectomy and is partly lost in the alcoholic because of accelerated gastric emptying and decreased gastric ADH activity, respectively. The latter is also lower in women than in men, at least below the age of 50. Some ADH isozymes require a relatively high ethanol concentration for optimal activity; therefore, the concentration of alcoholic beverages affects the amount metabolized. Fasting strikingly decreases FPM, most likely because of accelerated gastric emptying, resulting in shortened exposure of ethanol to gastric ADH and its more rapid intestinal absorption. Commonly used drugs, such as aspirin, acetaminophen and some H2-blockers decrease gastric ADH activity in vitro and produce increased blood alcohol levels in vivo, particularly at a low alcohol dose, equivalent to social drinking. Effects at higher ethanol dosage are still the subject of controversy. However, not all subjects display significant FPM, and published negative reports with H2 blockers do not specify whether first pass metabolism was present to begin with; some of the negative investigations also used dilute concentrations of alcohol, shown to minimize gastric metabolism. Thus, the stomach can metabolize amounts of ethanol of clinical relevance, an effect which is attenuated by various drugs, resulting in increased blood levels.

Adult↗
PubMed1994

Susceptibility to alcohol-related liver injury.

Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of ethanol-induced septal fibrosis and cirrhosis; its dilinoleoyl species also increases collagenase activity in lipocytes. The efficacy of this compound in man is now being studied in randomized multicenter clinical trials.

Acetaldehyde↗
PubMed1993

Hepatitis C virus antibody in alcoholic patients. Association with the presence of portal and/or lobular hepatitis.

OBJECTIVE: To evaluate the relationship between hepatitis C viral infection and alcoholic liver disease. DESIGN: Case-comparison study. SETTING: Bronx (NY) Veterans Affairs Medical Center. PARTICIPANTS: Forty-seven consecutive alcoholic patients undergoing diagnostic liver biopsy. MAIN OUTCOME MEASURES: Serum was obtained at the time of liver biopsy and assayed for antibodies to hepatitis C virus using enzyme-linked immunosorbent assay, recombinant immunoblot assay, and hepatitis C virus neutralization methods. RESULTS: Antibody to hepatitis C virus, as confirmed by the recombinant immunoblot assay, was strongly associated with the presence of portal and/or lobular inflammation (91% seropositivity) but was only present in 16% of patients without this histologic finding (P < .001). In patients without portal or lobular hepatitis, recombinant immunoblot assay seropositivity was seen in 27% of patients with cirrhosis and 20% of patients with alcoholic hepatitis and was absent in patients with steatosis and/or perivenular fibrosis. In the subgroup of alcoholic patients who were without known risk factors for hepatitis C virus infection (ie, no history of intravenous drug use or blood transfusions), antibody to hepatitis C virus was present in 78% of subjects with portal and/or lobular hepatitis but was absent in those with other types of alcoholic liver disease. Finally, anti-hepatitis C virus-seropositive patients had a significantly greater mean necroinflammatory score as compared with anti-hepatitis C virus-seronegative alcoholic patients (2.1 vs 1.2; P < .001). In contrast, there was no significant difference in the mean fibrosis score between the two groups. CONCLUSIONS: The presence of portal and/or lobular inflammation is strongly associated with antibodies to hepatitis C virus in alcoholic patients, even in the absence of known risk factors. This association indicates that hepatitis C virus is responsible, at least in part, for the portal and/or lobular hepatitis associated with alcoholic liver disease.

Adult↗
PubMed1993

In vivo induction of hepatic P4502E1 by ethanol: role of increased enzyme synthesis.

P4502E1 (2E1), an ethanol-inducible P450 enzyme, plays an important role in the bioactivation of certain hepatotoxins and chemical carcinogens. Different mechanisms of 2E1 induction by ethanol and other agents (e.g., acetone) have been proposed, ranging from enhanced de novo enzyme synthesis caused by an increase in 2E1 mRNA and/or the efficiency with which it is translated to decreased enzyme degradation stemming from substrate stabilization. To evaluate these mechanisms, we first examined the time course of hepatic 2E1 protein induction in rats pair-fed liquid diets containing 36% of total calories as either ethanol or dextrin-maltose (controls) for 28 days. Western blot analysis with anti-2E1 immunoglobulins revealed that 2E1 reached a new steady-state level (eightfold greater than that found with controls) after ethanol feeding for 10 days and remained elevated for the duration of treatment. Microsomal p-nitrophenol hydroxylation, a 2E1-catalyzed reaction, exhibited a similar induction time course, with the maximal increase in enzyme activity also observed on Day 10 of ethanol administration. We then determined steady-state 2E1 protein turnover in ethanol-fed and control animals that were given [35S]methionine plus[3H]aminolevulinate to radiolabel 2E1 apoprotein and the prosthetic heme group, respectively. Monophasic exponential decay curves showed that hepatic 2E1 protein and heme half-lives (27-28 h and 17 h, respectively) did not differ between the treatment groups. However, rates of 2E1 synthesis, assessed by measuring initial rates of incorporation of [35S]methionine and [3H]aminolevulinate into 2E1 apoprotein and heme, were increased in animals fed ethanol. Our results indicate that the in vivo induction of hepatic 2E1 protein by ethanol involves increased enzyme synthesis rather than decreased enzyme degradation. This enhancement of de novo 2E1 synthesis most likely entails the ethanol-mediated increase of steady-state levels of 2E1 mRNA and/or the stimulation of its translational efficiency.

Animals↗
PubMed1993

Aetiology and pathogenesis of alcoholic liver disease.

Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical carcinogens and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation and decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes glutathione depletion, free-radical mediated toxicity and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis: both in vivo and in vitro (in cultured myofibroblasts and lipocytes), ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding of the pathogenesis of alcoholic liver disease may eventually improve therapy with drugs and nutrients.

Deficiency Diseases↗
PubMed1993

Biochemical factors in alcoholic liver disease.

Three decades of research in ethanol metabolism have established that alcohol is hepatotoxic not only because of secondary malnutrition, but also through metabolic disturbances associated with the oxidation of ethanol. Some of these alterations are due to redox changes produced by the NADH generated via the liver ADH pathway, which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Exaggeration of the redox change by the relative hypoxia, which prevails physiologically in the perivenular zone, contributes to the exacerbation of the ethanol-induced lesions in zone III. Gastric ADH also explains first-pass metabolism by ethanol; its activity is low in alcoholics and in females and is decreased by some H2 blockers. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last 20 years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450 (P4502E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by P4502E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anesthetic agents, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion, but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes GSH depletion, free-radical-mediated toxicity, and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis; both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and lipocytes); ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding may eventually improve therapy with drugs and nutrients. Encouraging results have been obtained with some "super" nutrients. On the one hand, SAMe, the active form of methionine, was found to attenuate the ethanol-induced depletion in SAMe and GSH and associated mitochondrial lesions. On the other hand, phosphatidylcholine, purified from polyunsaturated lecithin, was discovered to oppose the ethanol-induced fibrosis by decreasing the activation of lipocytes to transitional cells, and possibly also by stimulating collagenase activity, an effect for which dilinoleoylphosphatidylcholine, its major phospholipid species, was found to be responsible.

Acetaldehyde↗
PubMed1993

Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver.

Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.

Alcoholic Intoxication↗
PubMed1993

Comparison of blood alcohol concentrations after beer and whiskey.

To determine whether blood alcohol concentrations achieved by ingestion of various alcoholic beverages differ as a function of prandial state, healthy male volunteers, aged 24 to 48 years, were given the same amount of alcohol (0.3 g/kg) as different beverages. The alcohol was consumed in three prandial states: postprandial (1 hr after a meal, n = 10), prandial (during the meal, n = 10), and preprandial (after an overnight fast, n = 9). Each subject was tested with both beer and whiskey, and in the postprandial state also with wine and sherry, in a within-subjects design. Blood alcohol concentrations were estimated by breath analysis for 4 hr or until concentrations reached zero. Peak blood alcohol levels were higher with beer than with whiskey in the postprandial and prandial conditions (p < 0.01), whereas the opposite was true in the preprandial state (p < 0.05). Similarly, the area under the blood alcohol curve was higher with beer in the prandial state (p < 0.05), and higher with whiskey in the preprandial condition (p < 0.01). Wine and sherry yielded peak concentrations intermediate between those of beer and whiskey in the postprandial state. The results indicate that a dilute alcoholic drink can yield either higher or lower blood alcohol levels than a concentrated beverage, depending on the prandial state.

Adult↗