Biliary permeability during ethinyl estradiol-induced cholestasis studied by segmented retrograde intrabiliary injections in rats

Abstract

The influence of ethinyl estradiol (EE) treatment on the permeability of the biliary tree in rats has been assessed by the segmented retrograde intrabiliary injection (SRII) technique. Three pairs of compounds were studied, inert [14C]sucrose and [3H]inulin; [14C]taurocholic acid (TC) and [14C]glycocholic acid (GC) and the non-ionic bile acid derivatives [125I]cholyldiglycylhistamine (CG2H) and [131I]cholyltetraglycylhistamine (CG4H). In control rats recovery in bile after SRII was always greater for the larger of any pair of compounds, confirming that the biliary tree acts as a filter, and that decreased recovery from bile during this technique is an index of greater biliary permeability. After EE treatment recovery of all compounds was significantly reduced, thus confirming that EE increases biliary permeability. Recovery of sucrose and inulin fell from 55-65% of the administered dose in controls to 8-9% in EE rats. Recoveries of TC, GC, CG2H and CG4H was also reduced, but their biliary recovery profiles were consistent with marked re-excretion into bile of that portion which had initially passed out of the biliary system by filtration. During the later phase of the experiment excretion of the negatively charged bile acids TC and GC was greater than that of the non-ionic bile acid derivatives CG2H and CG4H. Although the site at which these permeability changes have occurred is unknown, our results are compatible with previous data implicating increased tight junction permeability as a mechanism of EE-induced cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)