title: Management of carbon tetrachloride-induced acute liver injury in rats by syngeneic hepatocyte transplantation in spleen and peritoneal cavity.
abstract: OBJECTIVE
  Acute hepatitis may seldom have a fulminant course. In the treatment of this medical emergency, potential liver support measure must provide immediate and sufficient assistance to the hepatic function. The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx) in two different anatomical sites, splenic parenchyma and peritoneal cavity, in a rat model of reversible acute hepatitis induced by carbon tetrachloride (CCl(4)).
  
  
  METHODS
  After CCl(4) intoxication, 84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment: Group A (n=24): intrasplenic transplantation of 10x10(6) isolated hepatocytes, Group B (n=24): intraperitoneal transplantation of 20x10(6) isolated hepatocytes attached on plastic microcarriers, Group C (n=18): intrasplenic injection of 1 mL normal saline (sham-operated controls), Group D (n=18): intraperitoneal injection of 2.5 mL normal saline (sham-operated controls). Survival, liver function tests (LFT) and histology were studied in all four groups, on d 2,5 and 10 post-HCTx.
  
  
  RESULTS
  The ten-day survival (and mean survival) in the 4 groups was 72.2% (8.1+/-3.1), 33.3% (5.4+/-3.4), 0% (3.1+/-1.3) and 33.3% (5.4+/-3.6) in groups A, B, C, D, respectively (P(AB)<0.05, P(AC)<0.05, PBD=NS). In the final survivors, LFT (except alkaline phosphatase) and hepatic histology returned to normal, independently of their previous therapy. Viable hepatocytes were identified within splenic parenchyma (in group A on d 2) and both in the native liver and the fatty tissue of abdominal wall (in group B on d 5).
  
  
  CONCLUSIONS
  A significantly better survival of the intrasplenically transplanted animals has been demonstrated. Intraperitoneal hepatocytes failed to promptly engraft. A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.
authors.affiliation: Third Department of Propaudeutic Surgery, University of Athens, Sotiria Hospital, Athens, Hellas, Greece. hpilichos@hotmail.com
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pilichos
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
authors.forename: Maria
authors.initials: M
authors.lastname: Demonakou
authors.forename: Athena
authors.initials: A
authors.lastname: Preza
authors.forename: Ismini
authors.initials: I
authors.lastname: Donta
mesh_terms: D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology / Q000601:surgery*; D022781:Hepatocytes / Q000637:transplantation*; D008297:Male; D010529:Peritoneal Cavity / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000601:surgery*; D016019:Survival Analysis
chemical_list: D002251:Carbon Tetrachloride