Metabolism of sulfobromophthalein in jaundiced rat

We observed previously in humans that loading with BSP in obstructive jaundice resulted in elevated blood levels, of cysteine-conjugated BSP (Cyst-BSP). In order to clarify the mechanism of this phenomenon, an investigation was made into the origin of Cyst-BSP in rats with experimentally produced obstruction of bile duct (O-J). Using untreated rats as controls, the animals were determined for glutathione content and glutathione S transferase activity (GST) in liver cytosol. The influence of nephrectomy upon and the role of liver cell membrane in biodisposition of BSP were also investigated. The results are summarized as follows: 1) In the O-J group, the excretion in bile of glutathione-conjugated BSP (GSH-BSP) was markedly decreased. 2) O-J livers were found to have higher glutathione content and GST activity as compared to control livers. 3) Nephrectomy in O-J rats was followed by no gross change in the proportion of Cyst-BSP in blood and liver cytosol. 4) Following administration of individual liver cell membrane components change from GSH-BSP to Cyst-BSP was noted to occur only in O-J rats. These results led us to surmise that GSH-BSP accumulated in the liver in O-J is hydrolyzed to Cyst-BSP in the liver cell membrane.