Improvement of portal flow and hepatic microcirculatory tissue flow with N-acetylcysteine in dogs with obstructive jaundice produced by bile duct ligation

Abstract

Objective: To find out if N-acetylcysteine (NAC) would improve hepatic circulation in dogs with obstructive jaundice.

Design: Open laboratory study.

Setting: University hospitals, Japan and France.

Materials: 14 male beagle dogs and 10 male Wistar rats.

Interventions: Obstructive jaundice was produced by ligation of the common bile duct (CBD) for 7 days in both dogs and rats. Either 5% dextrose (control group, n = 7) or NAC (NAC group, n = 7) was given to dogs. Sinusoidal endothelial cells were obtained from rats after ligation by elutriation, and varying amounts of NAC were given.

Main outcome measures: The volumes of portal blood flow and hepatic microcirculatory tissue flow were reduced after ligation of the CBD, but those increased after NAC had been given to dogs with obstructive jaundice. NAC increased the concentrations of plasma cyclic 3',5'-guanosine monophosphate (cGMP). It also increased concentrations of serum and hepatic-reduced glutathione, and hepatic adenosine triphosphate (ATP) in cholestatic dogs, and secretion of cGMP from sinusoidal endothelial cells from rats with obstructive jaundice.

Conclusion: These results suggest that NAC given intravenously effectively improves hepatic circulation and hepatic function in dogs with obstructive jaundice.