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Studies on Hepatic Disorders pp 149–170Cite as

Oxidative Stress and Liver Ischemia–Reperfusion Injury

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Abstract

Hepatic ischemia/reperfusion (I/R) injury is a serious complication that compromises liver function because of extensive hepatocellular loss, which impacts diverse clinical settings such as liver surgery and liver transplantation. The mechanisms responsible for hepatic I/R injury are not well understood despite the identification of several intercellular and molecular mechanisms involved in the hepatocellular cell death, with a predominant role for reactive oxygen species (ROS) generation. Oxygen is a vital element to sustain life but its partial reduction generates toxic ROS that participate in liver I/R damage. Mitochondria are one of the main sources of ROS production in the cell, and current data point that mitochondrial dysfunction mediates hepatic I/R damage. In liver transplantation or in hepatic resections ischemia followed by reperfusion is accompanied by an increase in ROS generation leading to liver injury. The contribution of hepatic lipid composition, particularly lipid composition of mitochondrial membranes determine the increased ROS generation during hepatic I/R due to compromised mitochondrial antioxidant defenses. Accumulating evidence from clinical and experimental observations indicates that steatotic grafts in liver transplantation increase reperfusion injury and liver transplant failure. In this chapter we will review recent data on the interplay between mitochondria, ROS generation, and antioxidant defense in liver damage after I/R, and provide evidence that mitochondrial cholesterol accumulation stands as an important player in liver I/R damage, thus emerging as a novel target for intervention.

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Authors and Affiliations

  1. Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Científicas (CSIC) and Liver Unit-Hospital Clinic and Networked Biomedical Research Center for Hepatic and Digestive Diseases, Barcelona, 08036, Spain

    Carmen García-Ruíz

  2. Southern California Research Center for ALPD and Cirrhosis, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Carmen García-Ruíz & José C. Fernández-Checa

  3. Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council and Liver Unit-Hospital Clinic and CIBEREHD, Barcelona, 08036, Spain

    José C. Fernández-Checa

  4. Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona - Spanish National Research Council and Liver Unit-Hospital Clinic and Networked Biomedical Research Center for Hepatic and Digestive Diseases, Barcelona, 08036, Spain

    Albert Morales

Authors
  1. Carmen García-Ruíz
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  2. Albert Morales
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  3. José C. Fernández-Checa
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Corresponding authors

Correspondence to Carmen García-Ruíz or José C. Fernández-Checa .

Editor information

Editors and Affiliations

  1. Department of Health Sciences, University of Eastern Piedmont Amedeo Avogadro, Novara, Italy

    Emanuele Albano

  2. Department of Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, School of Medicine, University of Torino, Torino, Italy

    Maurizio Parola

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García-Ruíz, C., Morales, A., Fernández-Checa, J.C. (2015). Oxidative Stress and Liver Ischemia–Reperfusion Injury. In: Albano, E., Parola, M. (eds) Studies on Hepatic Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15539-5_7

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