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 6hr to 6d 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 6hr after two thirds hepatectomy and returned to normal 4d later. k₂ progressively decreased with a nadir at 2d, and returned to normal by 4d. k₃ was transiently depressed, and became normal within 2d. 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 1d after two thirds hepatectomy, and returned to normal by 6d. Unlike results for ³H‐bilirubin, there was a prolonged 50% reduction of k₂ and k₃ with return to normal by 6d. 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.