Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) were determined. PEP (100？mM) significantly prevented an increase in LDH leakage, histological changes, such as tubulonecrosis and vacuolization, and changes in oxidative stress parameters during 72？h of cold preservation in mouse liver. Although glucose (100？mM) partly prevented LDH leakage and histological changes, no effects against oxidative stress were observed. By contrast, NAC inhibited oxidative stress in the liver and did not prevent LDH leakage or histological changes. PEP also significantly prevented kidney damage during cold preservation in a dose-dependent manner, and the protective effects were superior to those of glucose and NAC. We suggest that PEP, a functional carbohydrate with organ protective and antioxidative activities, may be useful as an organ preservation agent in clinical transplantation. 1. Introduction Clinical transplantation, such as liver or kidney transplantation, is the only life-saving therapy for some severe diseases, such as end-stage kidney, liver failure, or chronic end-stage liver diseases. It is important to conserve the condition of the graft before transplantation because damage of the graft during cold preservation is one of the major risk factors for graft dysfunction. To solve this, organ preservation solutions, such as Euro-Collins solution and University of Wisconsin solution, are used [1, 2]. These solutions are generally composed of electrolytes and buffers, with carbohydrates, such as glucose and trehalose, added to prevent energy loss and increase the osmotic pressure of the solution. In addition, to inhibit the generation of reactive oxygen species during cold preservation and ischemia/reperfusion, antioxidants, glutathione and N-acetylcysteine, are added to the University of Wisconsin solution and ET-Kyoto solution, respectively [3, 4]. Although these solutions are essential for clinical transplantation, they have several disadvantages, including chemical instability and high viscosity. Additionally, they are not costeffective for short-term storage