Dynamic aspects of glutathione metabolism in obstructive jaundice.

The dynamic aspects of glutathione metabolism during obstructive jaundice were analyzed in rats. Plasma bilirubin levels increased after ligation of the bile duct, with a concomitant increase in hepatorenal glutathione levels. When the bile duct was recanalized, plasma bilirubin levels rapidly decreased, with a concomitant decrease in hepatorenal glutathione levels. The half-life of hepatic glutathione turnover increased markedly after bile duct obstruction, returning to normal after recanalization of the bile duct. Intravenous administration of a loading dose of bilirubin inhibited the biliary secretion of glutathione in a dose-dependent manner. On the other hand, renal glutathione efflux increased markedly after bile duct obstruction. These observations suggest that glutathione status is significantly affected in obstructive jaundice, predominantly due to the inhibition of hepatic secretion by increased bilirubin.