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Role of apoptosis in the remodeling of cholestatic liver injury following release of the mechanical stress

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Abstract

It has been known for a long time that portal fibrosis consecutive to experimental common bile duct ligation is reversible following obstacle removal, but the mechanisms involved remain unknown. We have studied the effect of bilioduodenal anastomosis and of simple biliary decompression on the remodeling of the lesion in bile duct-ligated rats. Rats were subjected to common bile duct ligation for 7 days or 14 days. Bilioduodenal anastomosis was performed after 14 days of bile duct ligation and animals sacrificed at intervals. In other animals, after 7 days or 14 days of ligation, the common bile duct was merely decompressed by bile aspiration and animals sacrificed 24 h later. Collagen deposition, α-smooth muscle actin expression and apoptosis were evaluated. Bile was collected and the bile acid profile assessed. After anastomosis, collagen deposition and α-smooth muscle actin expression decreased and were back to control values after 7 days. These parameters remained practically unchanged 24 h after biliary decompression. Bile duct ligation by itself induced apoptosis of some fibroblastic and bile ductular cells after 7 days; this was back to normal after 14 days. After anastomosis or decompression, apoptosis of both fibroblastic and bile ductular cells increased greatly and was accompanied by ultrastructural features of extracellular matrix degradation. Total bile acid content decreased after common bile duct ligation, the proportion of dihydroxylated bile acids decreasing and that of trihydroxylated bile acids increasing. Biliary decompression and anastomosis did not modify total concentration and composition of the biliary bile acid pool. In summary, we show that mere biliary decompression, by relieving the mechanical stress, is as effective as bilioduodenal anastomosis to induce apoptosis of portal cells that likely triggers portal fibrosis regression.

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Acknowledgements

This work was supported in part by the Région Aquitaine in France, by the Medical Research Council of Canada and by Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (Brazil). We thank the staff of the Biochemistry Department of Pellegrin Hospital (Bordeaux) for performing liver function tests.

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Authors and Affiliations

  1. Groupe de Recherches pour l'Etude du Foie, INSERM E0362, Université Victor Segalen Bordeaux 2, 146 rue Léo-Saignat, 33076 , Bordeaux cedex, France

    Andréa M. A. Costa, Thierry Lamireau, Charles Balabaud, Jean Rosenbaum & Alexis Desmoulière

  2. Departamento de Histologia e Embriologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Andréa M. A. Costa

  3. Département de Nutrition, Université de Montréal, Montréal, Canada

    Beatriz Tuchweber

  4. Département de Physiologie, Université de Montréal, Montréal, Canada

    Ibrahim M. Yousef

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  1. Andréa M. A. Costa
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  2. Beatriz Tuchweber
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  3. Thierry Lamireau
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  4. Ibrahim M. Yousef
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  5. Charles Balabaud
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  6. Jean Rosenbaum
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  7. Alexis Desmoulière
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Correspondence to Alexis Desmoulière.

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Costa, A.M.A., Tuchweber, B., Lamireau, T. et al. Role of apoptosis in the remodeling of cholestatic liver injury following release of the mechanical stress. Virchows Arch 442, 372–380 (2003). https://doi.org/10.1007/s00428-003-0773-7

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  • DOI: https://doi.org/10.1007/s00428-003-0773-7

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