Effects of edaravone, a radical scavenger, on hepatocyte transplantation

Background Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver‐based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte‐transplanted livers. Methods Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 106 cells were injected in a 1.0‐ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium‐only; Group B received HTx only; and Group C received HTx and edaravone. Forty‐eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide‐ and annexin‐V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post‐transplant days 0, 3, 5, 7, 10 and 14 using ELISA. Results The edaravone‐treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone‐treated liver sections also contained fewer TUNEL‐positive cells and animals that received edaravone had higher serum albumin levels post‐transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Conclusions Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application.