title: Sorafenib inhibits liver regeneration in rats.
abstract: BACKGROUND
  Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated.
  
  
  METHODS
  Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling.
  
  
  RESULTS
  Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8.
  
  
  CONCLUSIONS
  In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation.
authors: Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors: Kasper Jarlhelt
authors: KJ
authors: Andersen
authors: Anders Riegels
authors: AR
authors: Knudsen
authors: Anne-Sofie
authors: AS
authors: Kannerup
authors: Hideki
authors: H
authors: Sasanuma
authors: Jens Randel
authors: JR
authors: Nyengaard
authors: Stephen
authors: S
authors: Hamilton-Dutoit
authors: Morten
authors: M
authors: Ladekarl
authors: Frank Viborg
authors: FV
authors: Mortensen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D006498:Hepatectomy; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077157:Sorafenib; D013997:Time Factors
chemical_list: D019394:Ki-67 Antigen; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin