Development of intrahepatic cholestasis by alpha-naphthylisothiocyanate in rats

Development of intrahepatic cholestasis induced by alpha-naphthylisothiocyanate was studied in rats. At various times after alpha-naphthylisothiocyanate application, livers were isolated from treated rats and perfused hemoglobin-free to assess cholestatic parameters. Unstimulated bile flow was found to only slightly decrease up to 10 h after alpha-naphthylisothiocyanate administration. In contrast, secretion into bile of sulfobromophthalein and taurocholate declined markedly between 4 and 7 h as their concentrations in the perfusate increased, and stimulation of bile flow by taurocholate decreased. The permeability of the bile-to-perfusate barrier to [14C]sucrose and [32P]orthophosphate increased in parallel with the changes in sulfobromophthalein and taurocholate distributions. This correlation of changes in the distribution of cholephilic substances with biliary accessibility for extracellular markers suggests that, in alpha-naphthylisothiocyanate-induced cholestasis, increased leakage of tight junctions may contribute to regurgitation of bile constituents into the vascular system.