No increase of biliary permeability in ethinylestradiol-treated rats.

Ethinylestradiol, administered to male Wistar rats for 5 days (5 mg/kg X day), decreased bile flow in anesthetized animals and in isolated perfused livers. The bile salt secretion rate was diminished. The bile-to-perfusate ratios of [14C]sucrose and [14C]inulin increased significantly, but this could be attributed to the decline of bile flow as indicated by almost identical clearance rates. Theorectical analysis according to Forker and Wheeler yielded diffusion permeability coefficients (K) for sucrose and inulin of 0.243 and 0.037 in controls and 0.273 and 0.038 in ethinylestradiol-treated rats. In contrast, 9 h of alpha-naphthylisothiocyanate treatment (250 mg/kg) caused cholestasis with heavily decreased bile salt secretion rates. Here, K-values calculated for sucrose and inulin were 0.807 and 0.175. These findings suggest that altered permeability of the paracellular pathway is the cause for alpha-naphthylisothiocyanate-induced cholestasis, but not the primary event in ethinylestradiol-induced cholestasis.