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      Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review

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          Abstract

          The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.

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          Alcohol and mitochondria: a dysfunctional relationship.

          Mitochondria are intimately involved in the generation of and defense against reactive oxygen species (ROS). Mitochondria are themselves targets of oxidative stress and also contribute to mechanisms by which oxidative stress-related signals control cell fate. Ethanol promotes oxidative stress, both by increasing ROS formation and by decreasing cellular defense mechanisms. These effects of ethanol are prominent in the liver, the major site of ethanol metabolism in the body. The question remains to what extent this contributes to ethanol-dependent tissue damage or the susceptibility of cells to other stressors. In this review, we consider how mitochondrial actions of ethanol influence oxidative stress management of liver cells. Mitochondrial electron transport constitutes the major intracellular source of ROS, and ethanol treatment imposes conditions that promote ROS formation by mitochondria, the effects of which may be enhanced by a decrease in mitochondrial oxidative stress defenses. A significant target of ethanol-related increases in oxidative stress is mitochondrial DNA. Ethanol-induced damage to mitochondrial DNA, if not adequately repaired, impairs mitochondrial function, which further increases oxidative stress in the cell, leading to a vicious cycle of accumulating cell damage that is more apparent with advancing age. Uncontrolled mitochondrial formation of ROS promotes the inappropriate activation of the mitochondrial permeability transition, increasing the sensitivity of cells to other pro-apoptotic or damage signals. In combination with ethanol-induced defects in mitochondrial function, these alterations may promote both apoptotic and necrotic cell death in response to otherwise benign or beneficial challenges and contribute to the onset or progression of alcohol-induced liver diseases.
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            Mechanism of hypokalemia in magnesium deficiency.

            Magnesium deficiency is frequently associated with hypokalemia. Concomitant magnesium deficiency aggravates hypokalemia and renders it refractory to treatment by potassium. Herein is reviewed literature suggesting that magnesium deficiency exacerbates potassium wasting by increasing distal potassium secretion. A decrease in intracellular magnesium, caused by magnesium deficiency, releases the magnesium-mediated inhibition of ROMK channels and increases potassium secretion. Magnesium deficiency alone, however, does not necessarily cause hypokalemia. An increase in distal sodium delivery or elevated aldosterone levels may be required for exacerbating potassium wasting in magnesium deficiency.
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              Copper and Zinc Dysregulation in Alzheimer’s Disease

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                07 April 2019
                April 2019
                : 24
                : 7
                : 1361
                Affiliations
                [1 ]Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; jacek.baj@ 123456me.com (J.B.); maciejewski.r@ 123456gmail.com (R.M.)
                [2 ]Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, 20-090 Lublin, Poland
                [3 ]Department of Analitical Chemistry, Medical University of Lublin, 20-090 Lublin, Poland; bayrena@ 123456o2.pl
                [4 ]Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; mierzwinska.aa@ 123456gmail.com (A.M.); brzozowskak@ 123456gmail.com (K.B.); aforma@ 123456o2pl (A.F.)
                Author notes
                Author information
                https://orcid.org/0000-0002-2938-885X
                https://orcid.org/0000-0002-1372-8987
                Article
                molecules-24-01361
                10.3390/molecules24071361
                6480471
                30959950
                b720d5b6-e97d-48ca-bcec-a6478b33fdfe
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 March 2019
                : 06 April 2019
                Categories
                Review

                alcoholism,alcoholic liver disease,iron,magnesium,copper,manganese,deficiency

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