BILE SECRETION BY THE RAT-LIVER DURING SYNCHRONIZED REGENERATION

Simultaneous coexistence of differentiated, proliferating and rediffer entiated hepatocytes occurs during normal liver regeneration (LR). The aim of the present work was to study the time course of the capacity of the liver to form bile during synchronized LR. Following two-thirds partial hepatectomy (PH) in rats, i.v. administration of the ribonucl eotide reductase reversible inhibitor hydroxyurea (HU) was used to tra nsiently block liver cells at G1/S boundary. Experiments were performe d at 0 and 4 hours, and 1, 3 or 7 days after releasing HU-induced inhi bition. Bile acid pool size was determined by collecting bile samples over 24 hours. Initial (first hour) bile flow and bile acid output wer e increased early on during synchronized LR as compared with the value s found in non-hepatectomized control animals. These values were there after (1 day) reduced, but increased again at 3 days after halting HU infusion. The time course of bile acid depletion and changes in bile f low were very similar in control and synchronized LR, except that in t he latter a more important early reduction in bile flow and bile acid output was found. Shortly after PH, part of the bile acid pool was los t, but this was quickly restored, soon (1 day) reaching a net bile aci d pool size very similar to that found in control rats. The highest po ol size relative to liver weight was found on day 1, when bile acid ou tput and bile flow reached their lowest values. Additional experiments were performed using in situ perfused regenerating rat livers in whic h stepwise infusion of taurocholate (TC) was carried out. PH alone mod ified neither the bile acid-independent (BAIF) nor the bile acid-depen dent fraction of bile flow (BADF). However, in normal LR, the BAIF dec reased on day 1 and recovered at 7 days, while in synchronized LR it r emained depressed up to 7 days. The BADF was only reduced during the e arly phase of normal LR and did not change significantly in synchroniz ed LR. The maximal secretion rate (SRmax) for TC, as expressed per gra m of remaining liver tissue, was not affected immediately after PH, bu t a marked reduction was observed on day 1 in both normal and synchron ized LR. Afterwards, SRmax was quickly restored in both synchronized L R and, although in a slower way, normal LR. These results suggest that synchronization of LR involves changes in the time required to the re covery of specific liver functions such as bile formation.