Effect of Nafenopin on the Uptake of Bilirubin and Sulfobromophthalein by Isolated Perfused Rat Liver

Hepatic uptake of bilirubin and sul f obromophthalein has kinetic characteristics suggesting facilitated diffusion. Because these compounds demonstrate mutual competition for uptake, a shared uptake mechanism has been presumed. Previous studies in isolated perf used regenerating liver revealed depressed uptake of bilirubin, sul f obromophthalein, and asialoorosomucoid, a desialylated glycoprotein which enters hepatocytes by receptor-mediated endocytosis. This study was designed to determine whether or not depressed transport seen in liver regeneration occurs in other states of hepatocellular proliferation. Rats were pretreated with na f enopin (200 mg/kg ° day × 2), a drug that causes rapid hepatocellular proliferation similar to that seen in regeneration. Twenty-four hours after na f enopin treatment, liver weight increased by 40%. Influx, efflux, and sequestration rate constants in isolated perf used liver were quantitated by a computer fit to the model of Goresky. Results 1 day after na f enopin treatment revealed no change in transport parameters for bilirubin and asialoorosomucoid, but 55% and 49% reductions in influx of sul f obromophthalein and conjugated bilirubin, respectively. These studies suggest that hepatocellular proliferation alone is not responsible for the transport alterations seen during liver regeneration. Na f enopin effectively unmasks differences in uptake of bilirubin and other more water soluble organic anions such as sul f obromophthalein and conjugated bilirubin, suggesting that their uptake mechanisms are partially independent.