6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chronic alcohol consumption is a well-known risk factor for tissue injury. The link between alcohol use disorder (AUD) and kidney injury is intriguing but controversial, and the molecular mechanisms by which alcohol may damage the kidneys are poorly understood. Epidemiological studies attempting to link AUD and kidney disease are, to date, inconclusive, and there is little experimental evidence directly linking alcohol consumption to kidney injury. However, studies conducted primarily in other organs and tissues suggest several possible mechanisms by which alcohol may promote kidney dysfunction. One possible mechanism is oxidative stress resulting from increased production of reactive oxygen species, which leads to an excessive amount of free radicals, which in turn trigger tissue injury and increase inflammation. In addition, AUD’s effect on other major organs (liver, heart, intestines, and skeletal muscle) appears to promote unfavorable pathological processes that are harmful to the kidneys. Notably, these mechanisms have not yet been validated experimentally in the kidney. Additional research is needed to clarify if alcohol does indeed promote kidney injury and the mechanisms by which alcohol-induced kidney injury may occur.

          Related collections

          Most cited references55

          • Record: found
          • Abstract: found
          • Article: not found

          CYP2E1 and oxidative liver injury by alcohol.

          Ethanol-induced oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway seems to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide and, in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This review article summarizes some of the biochemical and toxicological properties of CYP2E1 and briefly describes the use of cell lines developed to constitutively express CYP2E1 and CYP2E1 knockout mice in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help us to understand the actions of CYP2E1 and its role in alcoholic liver injury.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Drug-induced mitochondrial dysfunction and cardiotoxicity.

            Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Györgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              The commonest glomerulonephritis in the world: IgA nephropathy.

              G D'Amico (1987)
                Bookmark

                Author and article information

                Journal
                Alcohol Res
                Alcohol Res
                Alcohol Research : Current Reviews
                National Institute on Alcohol Abuse and Alcoholism
                2168-3492
                2169-4796
                2017
                : 38
                : 2
                : 283-288
                Affiliations
                Zoltan V. Varga, M.D., Ph.D., is a visiting Research Fellow; Csaba Matyas, M.D., is a visiting Research Fellow; Janos Paloczi, Ph.D., is a visiting Research Fellow; and Pal Pacher, M.D., Ph.D., is a Senior Investigator and Lab Chief, all in the Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
                Article
                arcr-38-2-283
                5513691
                28988579
                11ceb764-c75a-498b-9e6a-a50b2f322130
                Copyright @ 2017

                Unless otherwise noted in the text, all material appearing in this journal is in the public domain and may be reproduced without permission. Citation of the source is appreciated.

                History
                Categories
                Articles

                alcoholic nephropathy,nephrotoxicity,acetaldehyde,proteinuria,glomerular filtration rate (gfr),glomerulonephritis,alcohol use disorder (aud),kidney injury

                Comments

                Comment on this article