Hepatocellular uptake of cyclodextrin-complexed curcumin during liver preservation: A feasibility study

摘要

The increasing demand for donor organs and the decreasing organ quality is prompting research toward new methods to reduce ischemia reperfusion injury (IRI). Several strategies have been proposed to protect preserved organs from this injury. Before curcumin/dextrin complex (CDC), a potent antioxidant and anti-inflammatory agent, can be used clinically we need to better understand the intracellular uptake under hypothermic conditions on a rat model of liver donation after circulatory death (DCD) and brain death (DBD). To be able to use the fluorescence of CDC for quantification the stability of CDC in different preservation solutions at 4 degrees C or 37 degrees C was investigated. Livers from Wistar rats were procured after being flushed-out through the portal vein using CDC-enriched preservation solutions and stored at 4 degrees C for variable periods. The CDC signal was stable in different preservation solutions over a period of 4h and allowed the rapid and lasting uptake of curcumin into cells. After 4h of preservation, CDC was no longer visible microscopically, and HPLC analysis showed very low to non-detectable tissue levels of CDC, proving metabolization during preservation. However, the distribution of CDC was not affected by warm ischemia damage (p=0.278) nor by flushing the livers before or after 4h of cold storage and without a warm preflush. Finally, curcumin reduced oxidative stress, lowered histological injury and did not change gene expression after WI/cold storage. Therefore, the use of CDC flush solution for the initial organ flush can offer a promising approach to the enhancement of liver preservation and the maintenance of its quality.