Effects of Cyclodextrin Curcumin Formulation on Ischemia-Reperfusion Injury in Porcine DCD Liver Transplantation

Abstract

Background.Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD). Methods.In a preclinical pig model of DCD-liver transplantation, livers exposed to 15' of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 mu mol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage. Area under the curve of log serum aspartate aminotransferase, markers of graft function (lactate, glycemia, prothrombin time, and bile production), inflammation (tumor necrosis factor-alpha), and survival were monitored. Results.Area under the curve of log serum aspartate aminotransferase were similar between curcumin and control groups (22.12 [20.87-24.88] versus 25.08 [22.1-26.55]; P = 0.28). No difference in the liver function markers were observed between groups except a lower serum lactate level 3-h post-reperfusion in the curcumin group (3 [1.95-6.07] versus 8.2 [4.85-13.45] mmol/L; P = 0.05). Serum tumor necrosis factor-alpha levels were similar in each group. Recipient survival rates were found similar. Conclusions.CDC added to the preservation solution in DCD liver pig model did not improve ischemia-reperfusion injury severity, liver function, or survival. Further efforts are needed to explore this strategy, particularly with dynamic preservation, which finds its way into clinical practice.