Inhibition of biliary excretion of indocyanine green by the thiol-oxidizing agent, diazenedicarboxylic acid bis[n,n′-dimethylamide]

Abstract Biliary excretion of Indocyanine green (ICG) in Sprague-Dawley rats during constant intravenous infusion of the dye in vivo was inhibited by intraperitoneally administered diazenedicarboxylic acid bis[ N , N ′-dimethylamide](diamide, 0.5 mmol/kg body wt), a glutathione-specific thiol-oxidizing agent. Significant inhibition of ICG excretion was observed also when ICG was injected rapidly 90 min after diamide administration. Disappearance of ICG from the plasma was not affected by diamide. Oxidized glutathione in bile increased transiently following diamide administration but returned to the basal level within 30 min. Hepatic concentrations of reduced and oxidized glutathione were not different from those of controls when determined 90 min after diamide administration. The inhibition of ICG excretion was completely prevented by subsequent administration of dithiothreitol (0.5 mmol/kg) 30 min after that of diamide. The results, therefore, suggest that the biliary excretion of ICG was inhibited by secondary changes in the redox status of thiols in hepatocytes caused by a transient increase in oxidized glutathione.