Reversible cholestasis induced by experimental partial obstruction of the bile duct: Biochemical, morphometric and hepatic transport kinetic studies

Abstract

The aim of this investigation was to reproduce in rats a partial stenosis of the common bile duct to analyze early liver functional and morphometric changes. The hepatic transport kinetics of sulfobromophthalein (organic anion) and rhodamine B (organic cation) was also investigated, and compartmental analysis of both compounds was performed. The humoral parameters of liver function indicated a cholestasis after 2 days of surgery, which reverted to reach normal values on the seventh day. Tumor necrosis factor alpha serum levels showed a tendency to increase on the second day of stenosis (7 out of 14 rats) while white blood cells increased on the second day of stenosis, and turned to normal levels on the seventh day. Histological studies showed increased volume of portal areas and ductular proliferation, which did no revert during the time of the study (up to 7 days post-op). Conversely, a moderate fibrosis and leukocyte infiltrates in portal areas predominated on the second day of stenosis, but normalized on the seventh day. Bile flow was considerably diminished on the second day of partial obstruction as compared to controls. The mean recovery in bile of sulfobromophthalein after 1 h of being injected was low on the second day of stenosis, but normalized on the seventh day. Conversely, that of rhodamine B was very low in all animals. Sulfobromophthalein kinetics showed that hepatic uptake and canalicular excretion were impaired during the second but normalized on the seventh day of stenosis. However, rhodamine B kinetics showed that this compound was poorly excreted in all groups although canalicular excretion increased on the second day. The results suggested a model of obstructive cholestasis induced by the experimental stenosis of the bile duct which was not only reversible but also implicates the role of hepatic inflammation.