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HPB (Oxford). 2013 Dec;15(12):944-50. doi: 10.1111/hpb.12068. Epub 2013 Mar 6.

Sorafenib inhibits liver regeneration in rats.

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1
Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

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.

CONCLUSION:

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.

PMID:
23461776
PMCID:
PMC3843612
DOI:
10.1111/hpb.12068
[Indexed for MEDLINE]
Free PMC Article
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