Enhanced prevention of cell death by hypothermic storage with propyl gallate

Current hypothermic preservation solutions are insufficient to prevent donor organ injury during hypothermic storage, which negatively impacts graft functional recovery and survival after transplantation. This study was to evaluate whether supplementation of the preservation solutions with antioxidant propyl gallates (PG) reduced cell injury during hypothermic storage and subsequently rewarming-reoxygenation or transplantation. Human cells and rat aorta were stored in University of Wisconsin (UW) or hyperbranched polyglycerol (HPG) solution supplemented with PG at 4 °C, followed by rewarming-reoxygenation with atmospheric O₂ at 37 °C and isotransplantation, respectively. Cell or tissue injury was measured by lactate dehydrogenase release, flow cytometric and histologic analyses. Here, we showed that PG supplementation significantly increased antioxidative activities of both UW and HPG solutions, and its concentrations for maximum protection of different human cells from hypothermic storage-induced cell death were estimated between 25 and 50 μM, which was also indicated by increased cell survival or decreased cell apoptosis during rewarming-reoxygenation. The PG cytoprotection was correlated with its inhibition of lipid peroxidation, prevention of mitochondrial dysfunction or an increase in ATP content. The enhanced cytoprotection of preservation solutions by PG supplementation was confirmed in hypothermic storage of rat aortas, indicated by less tissue damage and higher levels of tissue ATP during the hypothermic storage and less chronic injury after transplantation. In conclusion, cell injury during hypothermic storage and subsequently rewarming-reoxygenation was substantially prevented by the hypothermic preservation with PG, suggesting that PG is a promising antioxidant for hypothermic preservation of donor cells or organs in transplantation.