Ischemia reperfusion injury in aged livers - the energy metabolism, inflammatory response and autophagy

Abstract Due to the lack of adequate organs, the number of patients with end-stage liver diseases, acute liver failure or hepatic malignancies waiting for liver transplantation is constantly increasing. Accepting aged liver grafts is one of the strategies expanding the donor pool to ease the discrepancy between the growing demand and the limited supply of donor organs. However, recipients of organs from old donors may show an increased post-transplantation morbidity and mortality due to enhanced ischemia reperfusion injury. Energy metabolism, inflammatory response and autophagy are three critical processes which are involved in the ageing progress as well as in hepatic ischemia reperfusion injury. Compared to young liver grafts, impairment of energy metabolism in aged liver grafts leads to lower ATP production and an enhanced generation of free radicals, both aggravating the inflammatory response. The aggravated inflammatory response determines the extent of hepatic ischemia reperfusion injury and augments the liver damage. Autophagy protects cells by removal of damaged organelles including dysfunctional mitochondria, a process impaired in ageing and involved in ischemia reperfusion related apoptotic cell death. Furthermore, autophagic degradation of cellular compounds relieves intracellular ATP level for the energy depressed cells. Strategies targeting the mechanisms involved in energy metabolism, inflammatory response and autophagy might be especially useful to prevent the increased risk for ischemia reperfusion injury in aged livers after major hepatic surgery. CORRESPONDING AUTHOR: Uta Dahmen, M.D., Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Drackendorfer Straße 1, 07747 Jena, Germany. Telephone: +49-03641-932 5350; FAX: +49-03641-932 5352; E-mail: Uta.Dahmen@med.uni-jena.de AUTHORSHIP Kan C. (Chunyi.Kan@med.uni-jena.de) contributed to conception and design as well as participated in writing the article; Ungelenk L. (Luisa.Ungelenk@med.uni-jena.de) participated in the critical revision of the article; Lupp A. (Amelie.Lupp@med.uni-jena.de) participated in the critical revision of the article; Dirsch O. (Olaf.Dirsch@gmail.com) contributed to conception, design and obtain funding as well as participated in the critical revision of the article. Dahmen U. (Uta.Dahmen@med.uni-jena.de) contributed to conception, design and obtain funding as well as participated in the critical revision of the article. DISCLOSURE The authors disclose no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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