title: Effects of edaravone, a radical scavenger, on hepatocyte transplantation.
abstract: 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 × 10(6) 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.
authors.affiliation: Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Ryoutaro
authors.initials: R
authors.lastname: Ito
authors.forename: Akiko
authors.initials: A
authors.lastname: Murakumo
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Fox
authors.forename: Akihiko
authors.initials: A
authors.lastname: Horiguchi
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D022781:Hepatocytes / Q000637:transplantation*; D020287:In Situ Nick-End Labeling; D017114:Liver Failure, Acute / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000032:analysis; D013154:Spleen / Q000473:pathology
chemical_list: D012709:Serum Albumin; D000077553:Edaravone; D000983:Antipyrine
keywords: Edaravone; Hepatocyte; Radical scavenger; Transplantation