Increase in Paracellular Permeability as a Pathophysiological Principle of Drug-Induced Intrahepatic Cholestasis in Rats

  • H. Krell
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

Since the early studies on estrogen cholestasis (Forker, 1969), alterations in the permeability between canalicular and sinusoidal spaces have been regarded as a pathogenetic factor in drug-induced intrahepatic cholestasis. The general relevance of this alteration, however, was not clearly worked out. Isolated perfused livers pretreated with different drugs are a valuable tool to verify this concept. Thus, it was demonstrated that paracellular permeability to inert solutes such as sucrose and inulin was increased upon treating rats with α- naphthylisothiocyanate (ANIT, Krell et al., 1982) and estradiolvalerate (EV, Jaeschke et al., 1987a). Since it was observed that inert solutes were transported via transcellular pathways as well, quantitative determination was required of both transcellular and paracellular pathways of inert solutes into bile. This can be achieved by analyzing biliary off-kinetics of radioactive permeability markers after omission of the markers from the perfusion medium (Jaeschke et al., 1987b).

Keywords

Permeability Sucrose Ethyl Estrogen Estradiol 

References

  1. Forker EL (1969) The effect of estrogen on bile formation in the rat. J Clin Invest 48: 645–663CrossRefGoogle Scholar
  2. Krell H, Hoeke H, Pfaff E (1982) Development of intrahepatic cholestasis by alphanaphthylsothiocyanate in rats. Gastroenterology 82: 507–514PubMedGoogle Scholar
  3. Jaeschke H, Treummer E, Krell H (1987a) Increase in biliary permeability subsequent to intrahepatic cholestasis by estradiol valerate in rats. Gastroenterology 93: 533–538PubMedGoogle Scholar
  4. Jaeschke H, Krell H, Pfaff E (1987b) Quantitative estimation of transcellular and paracellular pathways of biliary sucrose in isolated perfused rat liver. Biochem J 241: 635–640PubMedGoogle Scholar
  5. Strasberg SM, Petrunka CN, Ilson RG, Paloheimo JE (1979) Characteristics of inert solute clearance by the monkey liver. Gastroenterology 76: 259–266PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • H. Krell
    • 1
  1. 1.Institut für Toxikologie der Universität TübingenTübingenGermany

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