1.
Zinc deficiency as a mediator of toxic effects of alcohol abuse.
Skalny, AV, Skalnaya, MG, Grabeklis, AR, Skalnaya, AA, Tinkov, AA
European journal of nutrition. 2018;(7):2313-2322
Abstract
OBJECTIVE To review data on the role of ethanol-induced alteration of Zn homeostasis in mediation of adverse effects of alcohol abuse. METHODS The scholarly published articles on the association between Zn metabolism and alcohol-associated disorders (liver, brain, lung, gut dysfunction, and fetal alcohol syndrome) have been reviewed. RESULTS It is demonstrated that alcohol-induced modulation of zinc transporters results in decreased Zn levels in lungs, liver, gut, and brain. Zn deficiency in the gut results in increased gut permeability, ultimately leading to endotoxemia and systemic inflammation. Similarly, Zn deficiency in lung epithelia and alveolar macrophages decreases lung barrier function resulting in respiratory distress syndrome. In turn, increased endotoxemia significantly contributes to proinflammatory state in alcoholic liver disease. Finally, impaired gut and liver functions may play a significant role in alcoholic brain damage, being associated with both increased proinflammatory signaling and accumulation of neurotoxic metabolites. It is also hypothesized that ethanol-induced Zn deficiency may interfere with neurotransmission. Similar changes may take place in the fetus as a result of impaired placental zinc transfer, maternal zinc deficiency, or maternal Zn sequestration, resulting in fetal alcoholic syndrome. Therefore, alcoholic Zn deficiency not only mediates the adverse effects of ethanol exposure, but also provides an additional link between different alcohol-induced disorders. CONCLUSIONS Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders.
2.
Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.
Neuman, MG, French, SW, Zakhari, S, Malnick, S, Seitz, HK, Cohen, LB, Salaspuro, M, Voinea-Griffin, A, Barasch, A, Kirpich, IA, et al
Experimental and molecular pathology. 2017;(1):162-180
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Abstract
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.
3.
[The efficacy of remaxol addition in the treatment of alcohol withdrawal syndrome].
Vinnikova, MA, Utkin, SI, Nenasteva, AY, Zakharov, MV
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2016;(1):40-46
Abstract
OBJECTIVE To study the efficacy of remaxol addition in the treatment scheme of alcohol withdrawal syndrome. MATERIAL AND METHODS Eighty patients with alcohol dependence and physical symptoms of alcohol withdrawal syndrome were enrolled. All patients received basic therapy in accordance to the applicable standards of treatment. The patients were randomized to remaxol introduced intravenously 2 times a day (morning and afternoon) in dose of 400 ml for 7 days (n=40) and saline with 25%-magnesium sulfate (10 ml) and 4% potassium chloride (10 ml) (n=40). RESULTS The effectiveness of the inclusion of remaxol was expressed in a more rapid relief of asthenic syndrome, reduction of phenomena such as tension, dysphoria, headache and impaired coordination of samples. Patients treated with remaxol demonstrated a trend towards a more rapid reduction of the affective (p=0.08) and behavioral components (p=0.09) of the syndrome of pathological craving for alcohol. Hepatoprotective and detoxification properties of the drug were confirmed by the significant decline in ALT and AST activity to the 20th day of treatment. Significant positive changes in lipid metabolism (HDL to the 7th day of treatment) and a normalizing effect on the processes of tissue respiration were shown as well. No adverse effects were noted. CONCLUSION The data obtained allow to recommend the inclusion of remaxol in the complex treatment regimens of alcohol withdrawal syndrome to improve the treatment efficacy.
4.
[Alcoholic ketoacidosis: not rare cause of metabolic acidosis].
Sibaï, K, Eggimann, P
Revue medicale suisse. 2005;(32):2106, 2108-10, 2112-5
Abstract
Alcoholic ketoacidosis is an often overlooked disorder, which affects chronic ethanol abusers who have usually had a binge culminating in severe vomiting with resulting hypovolemia, acute starvation and then a beta-hydroxybutyrate dominated ketoacidosis (due to the conjonction of enhanced Glucagon/Insuline and NADH/NAD ratios). Although the pathophysiology is complex, the syndrome is quickly reversible with the administration of saline and glucose solutions along with the correction of electrolyte disturbances, often unmasked during the treatment. Insuline and bicarbonates are not indicated. The prognosis, which is excellent, depends mainly on the coexisting acute disorders, which should be purchased and treated appropriately.