propylthiouracil and Alcoholism

Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.

Topics: Acetylcysteine; Adrenal Cortex Hormones; Alcoholism; End Stage Liver Disease; Enteral Nutrition; Hepatitis, Alcoholic; Humans; Immunity, Innate; Inflammation; Liver Transplantation; Pentoxifylline; Propylthiouracil; S-Adenosylmethionine; Treatment Outcome

Genetically mediated sensitivity to the bitter taste of phenylthiocarbamide (PTC) and 6-n-propylthiouracil (Prop) has long been associated with enhanced sensitivity to other sweet and bitter compounds. New studies suggest that tasters and supertasters of Prop may also differ from notasters in their taste preferences and in their patterns of food rejection and food acceptance. One question is whether the acceptability of bitter-tasting vegetables is influenced by Prop taster status. Cruciferous vegetables are among the major dietary sources of potentially chemoprotective agents in cancer control, and their consumption is reported to alter cancer risk. Strategies aimed at dietary change in individuals or groups should consider the role of genetic taste markers and their potential influences on food preferences and dietary habits.

Topics: Alcoholism; Food Preferences; Genetic Markers; Humans; Neoplasms; Nutritional Physiological Phenomena; Phenylthiourea; Propylthiouracil; Risk Factors; Taste; Vegetables

Topics: Alcoholism; Anabolic Agents; Colchicine; Enteral Nutrition; Ethanol; Female; Food, Formulated; Glucagon; Hepatitis, Alcoholic; Humans; Insulin; Liver; Male; Methylprednisolone; Nutrition Disorders; Prednisone; Propylthiouracil

The ability to taste 6-n-propylthiouracil (PROP) as bitter is determined genetically. The present study investigated whether this genetic ability was correlated with alcoholism and/or depression. Four groups of community college students (n = 25 each) were constituted based on the presence or absence of alcoholism and/or depression in themselves or their parents. Family history was assessed using the Family History-Research Diagnostic Criteria. Each subject was given a taste test using paper saturated with PROP. The results showed that subjects who had only alcoholism in their family were more likely to be nontasters of PROP than the control group, whereas subjects with both alcoholism and depression in their family were more likely to be so-called supertasters of PROP; that is, they found it extremely bitter. These findings suggest that PROP tasting might function as a genetic marker for two types of alcoholism.

Topics: Adolescent; Adult; Alcoholism; Depressive Disorder; Female; Genetic Markers; Hormone Antagonists; Humans; Male; Middle Aged; Propylthiouracil; Psychiatric Status Rating Scales; Taste

A 47-year-old man who smelled of alcohol presented with a three-day history of sore throat. He had not had fever, nausea, vomiting, diarrhea, rhinorrhea, cough, chest pain, or palpitations. On evaluation in the emergency department, he was found to have tachycardia and an irregular pulse.

Topics: Alcoholism; Antithyroid Agents; Atrial Fibrillation; Coxsackievirus Infections; Diagnosis, Differential; Electrocardiography; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests

Pelchat and Danowski [Physiol. Behav. 1992;51:1261-1266] reported an association between the ability to taste 6-n-propylthiouracil (PROP) and a parental history of alcoholism. Kranzler et al. [Alcohol Clin. Exp. Res. 1996a;20:1496-1500] previously failed to replicate these findings in a sample of subjects with only a paternal history of alcohol dependence. The present study was conducted to examine this putative association in a sample of subjects that is heterogeneous with respect to parental alcoholism history. Among the 90 alcohol-dependent subjects studied, the proportion of PROP nontasters was comparable to that observed among nonalcoholics. Analysis revealed no association of parental history with PROP taster status, even after controlling for potential confounding variables. We conclude that no reliable association exists between taste sensitivity to PROP and either a diagnosis of alcohol dependence or a parental history of alcohol dependence.

Topics: Adult; Alcoholism; Child of Impaired Parents; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Predictive Value of Tests; Propylthiouracil; Taste; Taste Threshold

Taste sensitivity to bitter substances, including ethanol, may play a moderating role both in the initiation of drinking and in the intensity and frequency of drinking once it is initiated. A study (Pelchat and Danowski, Physiol Behav 51:1261-1266, 1992) showed an association between the capacity to taste PROP (6-n-propylthiouracil), a bitter tasting compound, and a family history of alcoholism. The implication of that finding is that family-history-negative individuals may be protected from early initiation of drinking or heavy consumption of alcohol once drinking is initiated. The present study sought to replicate those findings by using direct interview methods (versus history methods) to obtain alcohol use and alcohol problem information from the parents of "at risk" individuals and by examining a larger number of subjects. A bimodal distribution of the ability to taste PROP was found, similar to that observed in the general population. No association was found between the ability to taste PROP and a paternal history of alcoholism, regardless of the taste threshold employed or after controlling for several potentially confounding variables. A lack of association with alcoholism risk was also observed for subjects' self-reports of reasons for drinking or not drinking alcohol based upon taste preference: high-risk and low-risk for alcoholism groups were not distinguished by either a stated preference for the taste of alcohol as a reason for drinking or a stated dislike for the taste of alcohol as a reason for limiting drinking. Thus, neither taste sensitivity for PROP nor the palatability of ethanol appear to influence the choice to drink among adolescent and young adult individuals at high risk for developing alcohol-related problems.

Topics: Adolescent; Adult; Alcoholism; Child of Impaired Parents; Female; Genetic Markers; Humans; Male; Propylthiouracil; Risk; Taste; Taste Threshold

Fifty-five young adult subjects and their parents were classified as alcoholic or nonalcoholic based on a standardized questionnaire (the MAST) filled out by the subjects. Subjects' thresholds for detection of 6-n-propylthiouracil (PROP; a PTC-like compound) were determined with the experimenter blind to MAST responses. There was a significantly higher proportion of nontasters of PROP among children of alcoholics than among children of nonalcoholics. There was no relationship between the child's alcoholism status and ability to taste PROP. These results are inconsistent with the view that excessive use of alcohol causes the association between nontasting and alcoholism and are consistent with the view that there is a genetic association between PROP/PTC-tasting and alcoholism.

Topics: Adolescent; Adult; Alcoholism; Female; Humans; Male; Propylthiouracil; Psychological Tests; Taste

With the aim to analyze whether propylthiouracil (PTU) alters ethanol-induced changes in liver iron and copper contents, 40 male albino mice were equally divided into a control group, an ethanol-treated group, a PTU-treated group and an ethanol + PTU-treated group. Twenty animals were killed at the age of 85 days and 20 at the age of 180 days. Liver iron and copper contents showed a progressive, statistically non-significant increase both in the controls and in ethanol-treated animals. Liver iron contents was significantly higher in the 180-day-old alcoholic mice as compared with controls. Animals treated either with PTU or with PTU + ethanol showed liver iron levels in the normal range, markedly different from the ethanol-treated animals (P less than 0.005). Liver copper content of the ethanol-treated animals was higher (but not significantly) than that of the controls. Liver copper levels of the PTU + ethanol-treated animals were in the range of the ethanol-treated animals. Thus, PTU seems to revert an overload of ethanol-mediated iron of copper.

Topics: Alcoholism; Animals; Copper; Ethanol; Iron; Liver; Male; Mice; Propylthiouracil

This report touched three aspects of drug therapy in alcoholics. The first topic consisted of a comparison between the effects of disulfiram treatment with the consequences of inborn deficiency of aldehyde dehydrogenase isozyme I; the comparison generated some concepts which might be subject to observational verification. The second topic was the citation of studies which suggest a selective decrease of the appetite for alcohol by drugs classified as serotonin uptake blockers. Finally, I cited the presently revealed success of propylthiouracil treatment of alcoholics suffering from liver damage, a success measured not only in laboratory terms but in terms of patient survival.

Topics: Alcoholism; Aversive Therapy; Disulfiram; Hepatitis, Alcoholic; Humans; Propylthiouracil; Serotonin Antagonists

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.

Topics: Adenosine Triphosphate; Alcohol Dehydrogenase; Alcohol Oxidoreductases; Alcoholism; Animals; Energy Metabolism; Ethanol; Humans; Liver; Liver Circulation; Liver Diseases, Alcoholic; NAD; Oxygen Consumption; Papio; Propylthiouracil; Rats; Sodium-Potassium-Exchanging ATPase; Thyroid Hormones

Alcoholism is a major health problem, and one of its primary manifestations is alcoholic liver disease. The mechanisms responsible for the various forms of alcoholic liver disease--fatty liver, alcoholic hepatitis, and cirrhosis--are at present poorly understood. Knowledge of these mechanisms is needed to provide a sound framework for the therapy and prevention of liver disease due to alcohol and for the identification of those individuals most susceptible to develop liver disease from alcohol abuse. These experiments were designed specifically to evaluate the postulate that ethanol-induced pericentral liver damage results from an accentuated gradient of decreasing oxygen tension leading to pericentral hypoxia. Microlight guides were used to detect NADH fluorescence, and miniature oxygen electrodes were employed to measure oxygen tensions from periportal and pericentral regions of the liver lobule from the perfused rat liver. With both techniques, ethanol treatment increased the hepatic oxygen gradient. This increase was blocked by the antithyroid drug propylthiouracil. Thus, these experiments provide evidence in support of the hypothesis that pericentral hypoxia is involved in the mechanism of ethanol-induced liver injury. Furthermore, low-flow hypoxia was shown to cause blebs in the pericentral region of the liver lobule in as little as 15 min. This surface blebbing could represent the mechanism for the well-known release of enzymes by impaired hepatic tissues.

Topics: Acetaldehyde; Alcohol Dehydrogenase; Alcohol Oxidoreductases; Alcoholism; Animals; Humans; L-Lactate Dehydrogenase; Liver; Liver Circulation; Liver Diseases, Alcoholic; Microscopy, Electron, Scanning; NAD; Oxygen Consumption; Propylthiouracil; Rats

In rats a single injection (330 mg/kg) of D-galactosamine significantly inhibited in vivo incorporation of 14C-amino acids into fibrinogen, seromucoids and total liver proteins, but not albumin, by one third. Prior chronic exposure to ethanol (5 g/kg/day for 6 weeks) potentiated the inhibition of synthesis of all protein fractions (including albumin) up to about 50%. Propylthiouracil had no beneficial but deleterious effect against this potentiation of hepatotoxicity.

Topics: Alcoholism; Animals; Blood Proteins; Chemical and Drug Induced Liver Injury; Galactosamine; Humans; Kinetics; Liver; Male; Propylthiouracil; Protein Biosynthesis; Rats; Rats, Inbred Strains

Topics: Alcoholism; Animals; Ethanol; Ferritins; Humans; Liver; Male; Propylthiouracil; Rats; Rats, Inbred Strains

Topics: Alcoholism; Animals; DNA; Ethanol; Humans; Liver; Male; Organ Size; Propylthiouracil; Rats

Administration of alcohol to rats through drinking water for 8 weeks produced a significant decrease in the liver vitamin A stores without causing any change in the plasma vitamin A levels. Treatment of the alcoholic rats with propylthiouracil for 2 weeks restored the liver vitamin A reserves to control levels.

Topics: Alcoholism; Animals; Humans; Liver; Male; Propylthiouracil; Rats; Vitamin A