Oncosis represents the main type of cell death in mouse models of cholestasis

J Hepatol. 2005 Mar;42(3):378-85. doi: 10.1016/j.jhep.2004.10.016.


Background/aims: Since the mechanisms leading to hepatocyte death in cholestasis are not well defined, we aimed to obtain closer insights into the related pathogenetic principles.

Methods: Cell death was assessed in common bile duct ligated (CBDL) and cholic acid (CA)-fed mice, and compared to Fas agonist Jo2-injected mice by studying H and E-stained tissue sections, DNA ladder analysis, caspase-3-like activity assay, immunohistochemistry, double immunofluorescence microscopy for activated caspase-3 and cytokeratin (CK) 18, the TUNEL method, and electron microscopy.

Results: Jo2-treated mice showed activation of caspase-3, breakdown of the CK intermediate filament network, and classical morphological features of apoptosis. In contrast, in CA-fed and CBDL mice, oncosis characterized by cell swelling and ruptured cell membranes was the predominant type of cell death, whereas in both experimental conditions significant activation of caspase-3 was absent and typical CK alterations were rare despite frequent positivity of the TUNEL assay.

Conclusions: (i) Oncosis represents the main type of hepatocyte death in acute cholestasis in mice. (ii) The importance of apoptosis in cholestasis may be overestimated if non-specific detection systems (e.g. TUNEL assay) are used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Aspartate Aminotransferases / blood
  • Bile Acids and Salts / blood
  • Bile Ducts / physiology
  • Cell Death*
  • Cell Membrane / pathology
  • Cholestasis / pathology*
  • Cholic Acid / toxicity
  • Disease Models, Animal
  • Hepatocytes / pathology
  • Hepatocytes / ultrastructure
  • Male
  • Mice


  • Bile Acids and Salts
  • Aspartate Aminotransferases
  • Cholic Acid