Relationship between biliary excretion of bilirubin and glutathione disulfide

The effects of two glutathione-oxidizing agents, t-butyl hydroperoxide and diamide, on biliary excretion of bilirubin and glutathione disulfide were investigated in anesthetized male Sprague-Dawley rats. Bilirubin (unconjugated) was infused at a constant rate of 100 nmol/kg/min through the jugular vein. When biliary excretion of bilirubin was stabilized, either of the glutathione-oxidizing agents was administered via the mesenteric vein. Biliary excretion of glutathione disulfide increased temporarily after the administration and returned to its basal levels within 20 min. The biliary excretion of bilirubin decreased during the same period and returned to the former levels thereafter. Changes in bile flow rates remained within 20% of the basal levels. A linear correlation was found between the increments in the bile concentration of glutathione disulfide and the decrements in that of bilirubin. Furthermore, separate experiments revealed that reduction of hepatocellular glutathione per se had little effect on biliary excretion of bilirubin. The results thus indicate that the reduction of biliary excretion of bilirubin by glutathione-oxidizing agents was due to the increase in biliary excretion of glutathione disulfide, and suggest that a common biliary excretory mechanism is shared, at least partially, by bilirubin and glutathione disulfide in Sprague-Dawley rats.