Bile salt transport after selective damage to acinar zone 3 hepatocytes by bromobenzene in the rat.

Bile Salt Transport after Selective Damage to Acinar Zone 3 Hepatocytes by Bromobenzene in the Rat, GUMUCIO, J. J., KATZ, M. E., MILLER, D. L., BALABAUD, C. P., GREENFIELD, J. M., AND WAGNER, R. M. (1979). Toxicol. Appl. Pharmacol. 50, 77-85. To quantitate the contribution of acinar zone 3 hepatocytes (centrilobular cells) to the transport of physiological concentrations of taurocholate, selective acinar zone 3 cell damage was induced in female rats by the administration of bromobenzene. Forty-eight hours later, livers were perfused in situ. Oxygen consumption, gluconeogenesis, transport of [%]taurocholate into bile, bile flow and capacity for removal of indocyanine green were assessed. The removal of single doses of [i4C]taurocholate injected into the portal vein at loads of 0.025 and 0.11 pmol/kg was then measured. Bromobenzene-treated livers removed 8&85 % of the injected dose while control livers removed about 98 %. The percentage of the injected dose removed by each group at each load of taurocholate remained fairly constant. In separate experiments, [‘%]taurocholate was administered in successive single injections at loads between 0.20 and 75 pmol/kg. The percentage of the injected dose removed remained constant and was similar to that observed at lower loads of taurocholate until a dose of 1 .O pmol/kg was used. At higher loads, the percentage of the injected dose removed decreased progressively, suggesting that the uptake process was reaching saturation. These results showed that acinar zone 3 hepatocytes contributed to the removal of 13-l 8 % of a physiological load of taurocholate. Furthermore, a 50 % decrease in bile flow was observed after bromobenzene administration. This suggested that damage to .the centrilobular area is followed by alterations in bile flow and by the passage of at least 13-18x of the bile salts reaching the acinus into the general circulation. In addition, taurocholate removal after carbon tetrachloride-induced damage to the centrilobular area was studied. Twelve to eighteen percent of the injected dose of [‘%]taurocholate was found in the hepatic vein effluent, values similar to the results obtained after bromobenzeneinduced damage.