Mini Review Clinical Research and Trials Clin Res Trials, 2019 doi: 10.15761/CRT.1000258 ISSN: 2059-0377 Volume 5: 1-4 Te role of oxidative stress in hepatic ischemia- reperfusion injury: potential target for interventions in liver transplantation Consuelo Orellana 1 , Rodrigo Villagrán 1 , Jonathan Zang 1 and Ramón Rodrigo 2 * 1 Medical students, Faculty of Medicine, University of Chile, Chile 2 Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile Abstract Liver transplantation is the defnitive therapy for most patients with end-stage liver failure. During this surgical procedure, hepatic ischemia-reperfusion is an unavoidable phenomenon known to be involved in graft injury, often resulting in postoperative complications and liver dysfunction. Although the pathophysiology behind ischemia reperfusion injury (IRI) comprises various mechanisms, oxidative stress (OS) has been recognized as a key factor. Te aims of this review are to provide an updated overview of the role of OS in liver IRI, providing some bases for therapeutic interventions based on counteracting the OS-related mechanism of injury and thus suggesting novel possible strategies in the prevention of IRI in liver transplants. *Correspondence to: Ramón Rodrigo, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile, E-mail: rrodrigo@med.uchile.cl Key words: ischemia-reperfusion, liver transplantation, oxidative stress, reactive oxygen species Received: April 19, 2019; Accepted: April 26, 2019; Published: April 30, 2019 Introduction Orthotopic liver transplantation (OLT) has become a lifesaving procedure for patients with end-stage liver disease or hepatocellular carcinoma. In this complex surgical process, reperfusion of the hypoxic tissue is an unavoidable phenomenon that aggravates the ischemic insult, causing harmful ischemic-reperfusion injury (IRI). Liver IRI is associated with postoperative graf dysfunction, transplant rejections and may increase the risk of organ failure [1]. Tis situation is a major problem, especially considering that there is a shortage of liver donors. Indeed, in 2018, 13,295 patients in the USA were waiting for a liver transplant, but only 8,250 procedures were performed, indicating a shortage of about 5,000 per year [2]. Tis plight has promoted the extension of donor organ criteria, so that suboptimal grafs, such as older, steatotic, dead-brain or non-heart-beating donors can be used for liver transplantation, as well as organs that have been subjected to prolonged periods of warm and cold storage [3]. However, these organs are particularly susceptible to IRI as a result of damage throughout the processes of procurement, preservation and surgery [4-8]. In summary, IRI not only contributes to the organ shortage (as organs might be deemed too damaged for the transplant) but also may damage remote vital organs [9], incur multiple organ failures, graf non-function, and acute or chronic rejection [10]. Despite the obvious clinical relevance of these data, the mechanisms accounting for organ IRI have not been elucidated [11,12]. Nevertheless, oxidative stress (OS) has been recognized as a key factor [13]. Te aims of this review are to present an updated outlook of the role of OS in liver IRI, providing some foundations for therapeutic interventions based on counteracting the OS-related mechanism of injury and thus suggesting novel possible strategies for prevention of IRI in liver transplants. Role of oxidative stress in liver transplantation Reactive oxygen species (ROS) are physiologically generated in an intrinsic way in every aerobic organism. In this process, mitochondria are the most important source of their production [14]. ROS comprises oxygen free radicals, such as hydroxyl radicals, peroxyl radicals, and superoxide anion, along with non-radicals like hypochlorous acid, hydrogen peroxide and ozone [15]. Tose compounds are able to cause damage to DNA as well as peroxidation of unsaturated fatty acids in cellular membranes, thus disrupting cellular integrity. Furthermore, lipid peroxyl radicals react with other lipids, nucleic acids and proteins, heightening damage [3]. To prevent this from occurring, there are endogenous defense mechanisms against ROS, which include enzymatic antioxidant defenses (such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)), and non- enzymatic compounds (beta-carotene, ascorbate, glutathione (GSH) and α-tocopherol). However, if ROS production increases enough to overwhelm the antioxidant defense system the cell undergoes oxidative stress. Tis can also happen if the cellular antioxidant systems are depleted [16]. During a liver transplant, the interruption of blood infow followed by reperfusion produces an abrupt increase in ROS, disrupting balance and causing oxidative stress and generally infammatory progressions. It has been shown that ROS are able to both trigger and modulate the allograf failure following OLT, by producing microvascular dysfunction and parenchymal injury [17]. Moreover, during the early stage of reperfusion, Kupfer cells (KC) are activated, modifying their morphology together with increasing ROS production [18]. In experimental models, ROS released from KC contribute to release infammatory mediators, trigger the process of