Chronic Alcohol (chronic + alcohol)

Distribution by Scientific Domains
Medical Sciences88%

Terms modified by Chronic Alcohol

  • chronic alcohol abuse
  • chronic alcohol consumption
    		•
  • chronic alcohol exposure
  • chronic alcohol feeding
    		•
  • chronic alcohol use

    • Selected Abstracts

    Betaine Protects Chronic Alcohol and ,-3 PUFA-Mediated Down-Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH

    ALCOHOLISM, Issue 3 2010
    Ravi Varatharajalu
    Background:, Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high ,-3 polyunsaturated fatty acids (,-3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects. Therefore, we investigated the influence of ETOH, ,-3 PUFA, and betaine on liver GSH, PON1 expression, lipid score, as well as serum PON1 and HCTLase activities. Methods:, Experimental rats belonging to various dietary groups were pair-fed with Lieber-DeCarli low (2.8% the dietary calories as ,3-fatty acids) and high (13.8% the dietary calories as ,3-fatty acids) menhaden fish alcohol-liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured. Results:, High ,-3 PUFA decreased liver PON1 mRNA expression, serum PON1, and HCTLase activity by 23% (p < 0.01), 20% (p < 0.05), and 28% (p < 0.05), respectively compared to the low ,-3 PUFA group. ETOH decreased PON1 mRNA expression by 25 and 30% (p < 0.01) with concomitant 27% (p < 0.05) and 38% (p < 0.01), decrease in liver GSH levels in low and high ,-3 PUFA groups, respectively. Correspondingly, serum PON1 activity decreased by 23% (p < 0.05) and 58% (p < 0.01) while serum HCTLase activity decreased by 25% (p < 0.05) and 59% (p < 0.01) in the low and high ,-3 PUFA ETOH groups, respectively. Betaine restored liver PON1 mRNA expressions in low and high ,-3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high ,-3 PUFA. Conclusions:, Based on these results, we conclude that dietary betaine not only atheroprotective by restoring liver GSH that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis. [source]

    Craving: what can be done to bring the insights of neuroscience, behavioral science and clinical science into synchrony

    ADDICTION, Issue 8s2 2000
    Roger E. Meyer
    Alcohol self-administration behavior is the common thread that is necessary to bring the insights of neuroscience, behavioral science and clinical science into synchrony around the concept of craving. Animal models should address the molecular and cellular changes that take place in behaviorally relevant brain regions of rats consequent to chronic self-administration of ethanol. Animal models can focus on the biology of the anticipatory state in alcohol preferring/consuming rats, as well as studies of the effects of possible medications on this state in the animal model, on actual alcohol consuming behavior, and on the residual effects of chronic alcohol on the non-human mammalian brain. In human studies of craving, cue-reactivity in the absence of the opportunity to drink alcohol does not have the same salience as cue-reactivity in which drinking is possible. Moreover, actual drinking behavior serves to validate self-reports of craving. Studies of limited alcohol self-administration in the laboratory are an essential element in screening new medications for the treatment of alcoholism. Studies to date suggest no adverse reaction to the participation of alcoholic subjects in limited alcohol self-administration studies, but the research community should continue to monitor carefully the outcomes of alcohol-dependent subjects who participate in this type of research, and efforts should always be made to encourage these subjects to enter active treatment. In outpatient clinical trials of new treatments for alcoholism, the assessment of craving should include queries regarding symptoms and signs of protracted abstinence such as sleep disturbances, as well as questions regarding situational craving. Field observations of alcoholics in their favorite drinking environments would contribute greatly to our understanding of the real-world phenomenology of craving. [source]

    Alcohol exposure and paracetamol-induced hepatotoxicity

    ADDICTION BIOLOGY, Issue 2 2002
    STEPHEN M. RIORDAN
    In contrast, serious hepatotoxicity at recommended or near-recommended doses for therapeutic purposes has been reported, mainly from the United States and in association with chronic alcohol use, leading to the widely held belief that chronic alcoholics are predisposed to paracetamol-related toxicity at relatively low doses. Yet the effects of alcohol on paracetamol metabolism are complex. Studies performed in both experimental animals and humans indicate that chronic alcohol use leads to a short-term, two- to threefold increase in hepatic content of cytochrome P4502E1, the major isoform responsible for the generation of the toxic metabolite from paracetamol, although increased oxidative metabolism of paracetamol at recommended doses has not been demonstrated clinically. A reduced hepatic content of glutathione, required to detoxify the reactive metabolite, has been documented in chronic alcoholics, due probably to associated fasting and malnutrition, providing a metabolic basis for any possible predisposition of this group to hepatotoxicity at relatively low paracetamol doses. Simultaneous alcohol and paracetamol ingestion reduces oxidative metabolism of paracetamol in both rodents and humans, predominantly as a consequence of depletion in cytosol of free NADPH. The possibilities that chronic alcohol use may predispose to paracetamol-related hepatotoxicity and that alcohol taken with paracetamol may protect against it, based on these metabolic observations, are examined in this review. [source]

    Acute and Chronic Alcohol Exposure Impair the Phagocytosis of Apoptotic Cells and Enhance the Pulmonary Inflammatory Response

    ALCOHOLISM, Issue 10 2010
    Darren M. Boé
    Background:, Alcohol abuse increases the risk for acute respiratory distress syndrome (ARDS). Efferocytosis, the clearance of apoptotic cells, is important in the resolution of inflammation and is regulated by RhoA and rho kinase (ROCK) activation. The effects of alcohol on pulmonary Rho pathway activation and efferocytosis have not been determined. We hypothesize that acute and chronic alcohol exposure impair pulmonary efferocytosis, leading to heightened inflammation during ARDS. Methods:, For in vivo experiments, C57BL/6 mice received either a single intraperitoneal injection of alcohol or chronic ethanol-in-water for 8 weeks prior to intratracheal instillation of apoptotic cells or lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed for cells counts, calculation of the phagocytic index (PI), and Rho activity measurements. For in vitro studies, primary alveolar macrophages were cultured in alcohol (25,100 mM) and then co-cultured with apoptotic cells. RhoA activity was determined following alcohol exposure, and the PI was determined before and after treatment with the ROCK inhibitor, Y27632. Results:, Acute alcohol exposure was associated with impaired efferocytosis. Following LPS exposure, acute alcohol exposure was also associated with increased BAL neutrophils. Chronic alcohol exposure alone did not alter efferocytosis. However, following exposure to LPS, chronic alcohol exposure was associated with both impaired efferocytosis and increased BAL neutrophils. In vitro alcohol exposure caused a dose-dependent decrease in efferocytosis. Despite the fact that RhoA activity was decreased by alcohol exposure and RhoA inhibition did not alter the effects of alcohol on efferocytosis, treatment with the Rho kinase inhibitor, Y27632, reversed the effects of alcohol on efferocytosis. Conclusions:, Acute alcohol exposure impairs pulmonary efferocytosis, whereas exposure to chronic alcohol is only associated with impaired efferocytosis following LPS-induced lung injury. Both forms of alcohol exposure are associated with increased alveolar neutrophil numbers in response to LPS. The acute effects of alcohol on efferocytosis appear to be mediated, at least in part, by RhoA-independent activation of ROCK. Further studies are needed to dissect the differences between the effects of acute and chronic alcohol exposure on efferocytosis and to determine the effects of alcohol on alternative activators of ROCK. [source]

    Betaine Protects Chronic Alcohol and ,-3 PUFA-Mediated Down-Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH

    ALCOHOLISM, Issue 3 2010
    Ravi Varatharajalu
    Background:, Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high ,-3 polyunsaturated fatty acids (,-3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects. Therefore, we investigated the influence of ETOH, ,-3 PUFA, and betaine on liver GSH, PON1 expression, lipid score, as well as serum PON1 and HCTLase activities. Methods:, Experimental rats belonging to various dietary groups were pair-fed with Lieber-DeCarli low (2.8% the dietary calories as ,3-fatty acids) and high (13.8% the dietary calories as ,3-fatty acids) menhaden fish alcohol-liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured. Results:, High ,-3 PUFA decreased liver PON1 mRNA expression, serum PON1, and HCTLase activity by 23% (p < 0.01), 20% (p < 0.05), and 28% (p < 0.05), respectively compared to the low ,-3 PUFA group. ETOH decreased PON1 mRNA expression by 25 and 30% (p < 0.01) with concomitant 27% (p < 0.05) and 38% (p < 0.01), decrease in liver GSH levels in low and high ,-3 PUFA groups, respectively. Correspondingly, serum PON1 activity decreased by 23% (p < 0.05) and 58% (p < 0.01) while serum HCTLase activity decreased by 25% (p < 0.05) and 59% (p < 0.01) in the low and high ,-3 PUFA ETOH groups, respectively. Betaine restored liver PON1 mRNA expressions in low and high ,-3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high ,-3 PUFA. Conclusions:, Based on these results, we conclude that dietary betaine not only atheroprotective by restoring liver GSH that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis. [source]

    Nitric Oxide-Mediated Intestinal Injury Is Required for Alcohol-Induced Gut Leakiness and Liver Damage

    ALCOHOLISM, Issue 7 2009
    Yueming Tang
    Background:, Alcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro- l -arginine methyl ester (l -NAME), l -N6 -(1-iminoethyl)-lysine (l -NIL)] in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH). Methods:, Male Sprague,Dawley rats were gavaged daily with alcohol (6 g/kg/d) or dextrose for 10 weeks ± l -NAME, l -NIL, or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity. Results:, Alcohol caused tissue oxidation, gut leakiness, endotoxemia, and ASH. l -NIL and l -NAME, but not the d -enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation, and liver injury. Conclusions:, The mechanism we reported for alcohol-induced intestinal barrier disruption in vitro , NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver injury , appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD. [source]

    Chronic Ethanol Feeding Alters Hepatocyte Memory Which is not Altered by Acute Feeding

    ALCOHOLISM, Issue 4 2009
    F. Bardag-Gorce
    Background:, Gene expression changes in the liver after acute binge drinking may differ from the changes seen in chronic ethanol feeding in the rat. The changes in gene expression after chronic ethanol feeding may sensitize the liver to alcohol-induced liver damage, which is not seen after acute binge drinking. Methods:, To test this hypothesis, gene microarray analysis was performed on the livers of rats (n = 3) fed an acute binge dose of ethanol (6 g/kg body wt) and killed at 3 and 12 hours after ethanol by gavage. The gene microarrays were compared with those made on the liver of rats from a previous study, in which the rats were fed ethanol by intragastric tube for 1 month (36% of calories derived from ethanol). Results:, Microarray analysis data varied between the acute and chronic models in several important respects. Growth factors increased mainly in the chronic alcohol fed rat. Changes in enzymes involved in oxidative stress were noted only with chronic ethanol feeding. Gene expression of fat metabolism was increased only with chronic ethanol feeding. Most importantly, epigenetic related enzymes and acetylation and methylation of histones changed only after chronic ethanol feeding. Conclusions:, The results support the concept that chronic ethanol ingestion induces altered gene expression as a result of changes in epigenetic mechanisms, where acetylation and methylation of histones were altered. [source]

    A Recent Perspective on Alcohol, Immunity, and Host Defense

    ALCOHOLISM, Issue 2 2009
    Gyongyi Szabo
    Background:, Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system. Methods:, Medline and Pubmed databases were used to identify published reports with particular interest in the period of 2000,2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity. Results:, This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed. Conclusion:, Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects. [source]