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Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.

Publication ,  Journal Article
Kohli, V; Selzner, M; Madden, JF; Bentley, RC; Clavien, PA
Published in: Transplantation
April 27, 1999

BACKGROUND: Ischemic injury of the liver is generally considered to result in necrosis, but it has recently been recognized that mediators of apoptosis are activated during ischemia/reperfusion. This study was designed to characterize the extent and the type of cells within the liver that undergo apoptosis at different periods of ischemia and reperfusion. METHODS: Male Wistar rats were subjected to 30 or 60 min of normothermic ischemia. Liver sections were evaluated at the end of ischemia and at 1, 6, 24, and 72 hr after reperfusion. Apoptosis was determined by DNA fragmentation as evaluated by laddering on gel electrophoresis, in situ staining for apoptotic cells using TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL), and morphology on electron microscopy. RESULTS: In situ staining of liver biopsy specimens using TUNEL showed significant apoptosis after reperfusion. Sinusoidal endothelial cells (SEC) showed evidence of apoptosis earlier than hepatocytes. For example, at 1 hr of reperfusion after 60 min of ischemia, 22+/-4% of the SEC stained TUNEL positive compared with 2+/-1% of the hepatocytes (P<0.001). With a longer duration of ischemia, a greater number of SEC and hepatocytes became TUNEL positive. An increase in TUNEL-positive cells was also noted with an increasing duration of reperfusion. The presence of apoptotic SEC and hepatocytes was supported by DNA laddering on gel electrophoresis and cell morphology on electron microscopy. Several Kupffer cells were seen containing apoptotic bodies but did not show evidence of apoptosis. Only rare hepatocytes showed features of necrosis after 60 min of ischemia and 6 hr of reperfusion. CONCLUSION: These results suggest that apoptosis of endothelial cells followed by hepatocytes is an important mechanism of cell death after ischemia/reperfusion injury in the liver.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

April 27, 1999

Volume

67

Issue

8

Start / End Page

1099 / 1105

Location

United States

Related Subject Headings

  • Surgery
  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Male
  • Liver Circulation
  • Liver
  • Ischemia
  • In Situ Nick-End Labeling
  • Endothelium, Vascular
 

Citation

APA
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ICMJE
MLA
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Kohli, V., Selzner, M., Madden, J. F., Bentley, R. C., & Clavien, P. A. (1999). Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation, 67(8), 1099–1105. https://doi.org/10.1097/00007890-199904270-00003
Kohli, V., M. Selzner, J. F. Madden, R. C. Bentley, and P. A. Clavien. “Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.Transplantation 67, no. 8 (April 27, 1999): 1099–1105. https://doi.org/10.1097/00007890-199904270-00003.
Kohli V, Selzner M, Madden JF, Bentley RC, Clavien PA. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation. 1999 Apr 27;67(8):1099–105.
Kohli, V., et al. “Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.Transplantation, vol. 67, no. 8, Apr. 1999, pp. 1099–105. Pubmed, doi:10.1097/00007890-199904270-00003.
Kohli V, Selzner M, Madden JF, Bentley RC, Clavien PA. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation. 1999 Apr 27;67(8):1099–1105.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

April 27, 1999

Volume

67

Issue

8

Start / End Page

1099 / 1105

Location

United States

Related Subject Headings

  • Surgery
  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Male
  • Liver Circulation
  • Liver
  • Ischemia
  • In Situ Nick-End Labeling
  • Endothelium, Vascular