Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration

The normal rat hepatocyte divides approximately once per year but, following two thirds hepatectomy, rapid cellular replication occurs throughout the remaining liver remnant. Using a multiple indicator dilution technique, single-pass transport of 3H-bilirubin and 125I-asialoorosomucoid was studied in isolated perfused liver from 6 hr to 6 d after two thirds hepatectomy or sham surgery. Influx (k1), efflux (k2), and sequestration (k3) rates were quantitated by computer analysis. k1 for 3H-bilirubin fell by over 50% within 6 hr after two thirds hepatectomy and returned to normal 4 d later. k2 progressively decreased with a nadir at 2 d, and returned to normal by 4 d. k3 was transiently depressed, and became normal within 2 d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k2 and k3 parameters for best fit. Similar to results for 3H-bilirubin, the k1 of 125I-asialoorosomucoid was 20% of normal at 1 d after two thirds hepatectomy, and returned to normal by 6 d. Unlike results for 3H-bilirubin, there was a prolonged 50% reduction of k2 and k3 with return to normal by 6 d. The transport changes during regeneration are independent of reduced liver mass or changes in hepatic spaces of distribution. The fact that influx of both compounds reaches a nadir at the time of greatest cellular proliferation with subsequent return to normal suggests a "maturation" of liver cell function for restoration of these specific hepatocyte functions. Modulation of the hepatocyte receptor for desialylated glycoproteins may also be required for cellular recognition as a prerequisite for proliferative responses.