Hepatic transport of indocyanine green in dogs chronically intoxicated with dimethylnitrosamine

Abstract

Hepatic transport of indocyanine green (ICG) was examined in dogs chronically intoxicated with dimethylnitrosamine (DMN) (2 mg/kg) intraportally once a week for 6 weeks. In pathophysiological consequences, significant increases ( p < 0.05) were shown in both glutamic-pyruvic transaminase (GPT) and total plasma bile acids, but no significant difference was shown in body weight, liver wet weight, glutamicoxaloacetic transaminase (GOT), plasma alkaline phosphatase activity, total plasma protein, and total plasma bilirubin. By histologic examination of livers from intoxicated dogs, increased fibrosis in periportal, perisinusoidal, and especially pericentral areas, with loss of normal architecture, was observed. Partial fibrous bridging between periportal and pericentral areas was also demonstrated, but extensive pseudolobulation with regenerative nodules was not observed. The portal venous pressure of the intoxicated dogs was increased by approximately 50% of that of control dogs. In intoxicated dogs, delays were shown in both plasma disappearance and biliary excretion of ICG and significant decreases were observed in the pharmacokinetic parameters k 12 (plasma to liver transfer rate constant), V 2 (distribution volume of liver compartment), and CL tot (total body-plasma clearance), while a significant increase was observed in k 23 (intrahepatic diffusion and transport rate constant); the V 1 (distribution volume of plasma compartment) was not altered. From these findings, it is suggested that the decrease in the intrinsic clearance of ICG for the hepatic uptake process might explain the decrease in ICG uptake rate into the liver which was observed in the DMN-intoxicated dogs. Dogs chronically intoxicated with DMN might be a good model for studying hepatic dysfunction.