Jens Randel Nyengaard

Sorafenib inhibits liver regeneration in rats

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Sorafenib inhibits liver regeneration in rats. / Andersen, K.J.; Knudsen, A.R.; Kannerup, A.-S.; Sasanuma, H.; Nyengaard, J.R.; Hamilton-Dutoit, S.; Ladekarl, M.; Mortensen, F.V.

In: H P B, Vol. 15, No. 12, 2013, p. 944-950.

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@article{3178cb9f24fa42729eac0df078c9e981,
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. 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.",
author = "K.J. Andersen and A.R. Knudsen and A.-S. Kannerup and H. Sasanuma and J.R. Nyengaard and S. Hamilton-Dutoit and M. Ladekarl and F.V. Mortensen",
year = "2013",
doi = "10.1111/hpb.12068",
language = "English",
volume = "15",
pages = "944--950",
journal = "H P B",
issn = "1365-182X",
publisher = "Elsevier Ltd",
number = "12",

}

RIS

TY - JOUR

T1 - Sorafenib inhibits liver regeneration in rats

AU - Andersen, K.J.

AU - Knudsen, A.R.

AU - Kannerup, A.-S.

AU - Sasanuma, H.

AU - Nyengaard, J.R.

AU - Hamilton-Dutoit, S.

AU - Ladekarl, M.

AU - Mortensen, F.V.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84887320102&partnerID=8YFLogxK

U2 - 10.1111/hpb.12068

DO - 10.1111/hpb.12068

M3 - Journal article

C2 - 23461776

AN - SCOPUS:84887320102

VL - 15

SP - 944

EP - 950

JO - H P B

JF - H P B

SN - 1365-182X

IS - 12

ER -