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

Abstract Increasing demand for donor organs and decreasing organ quality is prompting research toward new methods to reduce ischemia reperfusion injury (IRI). Several strategies have been proposed to protect the preserved organ 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 rat model of liver donation after circulatory death (DCD) and brain death (DBD). To be able to use the fluorescence of CDC for quantification we investigate the stability of CDC in different preservation solutions at 4°C or 37°C. Livers from Wistar rats were procured after being flush‐out through the portal vein using CDC‐enriched preservation solutions and stored at 4 °C for variable periods. CDC signal was stable in different preservation solutions over a period of 4 h and allowed rapid and lasting uptake of curcumin into cells. After 4 h 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 WI damage (p=0.278) nor by flushing the livers before or after 4 h of cold storage and not with 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 CD...
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL PAPER Source Type: research