Change of zonal bile acid processing after partial hepatectomy in the rat

The aim of this study was to analyze whether partial hepatectomy alters functional liver heterogeneity with respect to bile acid processing. One, 5 and 21 days after liver resection (≈8)% of liver mass) in male Sprague-Dawlye rats (300–400 g), isolated livers were perfused in either the antegrade or the retrograde direction, respectively, with 32 nmol cholate/min per g liver. Uptake, metabolism and biliary secretion kinetics were determined by bolus injection of 14C-cholate. Uptake and biliary recovery (within 30 mn) of cholate were >90% in all groups. One day postresection, liver mass had already doubled and it regenerated to over 80% 5 days after resection. Serum bile acid concentration increased rapidly, peaking 61 h after resection (176.7±28.5 μmol/l) (mean±SEM). Twenty-one days after resection it fell to control values (23.±3.8 μmol/l). T 25(T 50), the time (min) necessary to excrete 25% (50) of the bile acid load into bile, was strikingly different between periportal and pericentral cells of controls (1.8 vs 5.7 and 3.4 vs 8.1). Five days after resection this difference became smaller (1.4 vs 2.9 and 2.8 vs 5.5) due to accelerated biliary cholate secretion in pericentral cells. Pericentral cells of controls metabolized cholate more extensively to taurocholate (≈83%) and glycocholate (≈13%) than periportal cells of controls (65%, 10%), leading to a 5-fold higher proportion of unmetabolized cholate in periportal than pericentral cells (25% vs 5%). Five days after resection the percentage of taurocholate decreased significantly at the expense of an increased formation of glycocholate. Twenty-one days after resection, bile acid composition came to resemble that of controls. In conclusion, the results demosntrate a reduction of metabolic zonation with regard to bile acid processing after liver resection. Despite accelerated biliary bile acid secretion in pericentral cells of the regenerating liver, overall metabolism was not impaired as compared to controls. This is comparable to weaning rats where functional liver heterogeneity has not yet developed.