The greater vulnerability of bile duct cells to reoxygenation injury than to anoxia: Implications for the pathogenesis of biliary strictures after liver transplantation

K. Noack, S. F. Bronk, A. Kato, Gregory James Gores

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131 Citations (Scopus)

Abstract

The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalTransplantation
Volume56
Issue number3
StatePublished - 1993

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Bile Ducts
Liver Transplantation
Pathologic Constriction
Wounds and Injuries
Hepatocytes
Hypoxia
Poisons
Liver
Reperfusion Injury
Proteolysis
Allografts
Glutathione
Cell Survival
Epithelium
Epithelial Cells
Oxygen

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

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title = "The greater vulnerability of bile duct cells to reoxygenation injury than to anoxia: Implications for the pathogenesis of biliary strictures after liver transplantation",
abstract = "The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation.",
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T2 - Implications for the pathogenesis of biliary strictures after liver transplantation

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AU - Kato, A.

AU - Gores, Gregory James

PY - 1993

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N2 - The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation.

AB - The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation.

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