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Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration
Author(s) -
Gärtner Ulrich,
Stockert Richard J.,
Morell Anatol G.,
Wolkoff Allan W.
Publication year - 1981
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840010203
Subject(s) - bilirubin , hepatocyte , liver regeneration , hepatectomy , medicine , endocrinology , liver function , regeneration (biology) , biology , chemistry , biochemistry , surgery , microbiology and biotechnology , resection , in vitro
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 3 H‐bilirubin and 125 I‐asialoorosomucoid was studied in isolated perfused liver from 6hr to 6d after two thirds hepatectomy or sham surgery. Influx (k 1 ), efflux (k 2 ), and sequestration (k 3 ) rates were quantitated by computer analysis. k 1 for 3 H‐bilirubin fell by over 50% within 6hr after two thirds hepatectomy and returned to normal 4d later. k 2 progressively decreased with a nadir at 2d, and returned to normal by 4d. k 3 was transiently depressed, and became normal within 2d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k 2 and k 3 parameters for best fit. Similar to results for 3 H‐bilirubin, the k 1 of 125 I‐asialoorosomucoid was 20% of normal at 1d after two thirds hepatectomy, and returned to normal by 6d. Unlike results for 3 H‐bilirubin, there was a prolonged 50% reduction of k 2 and k 3 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.