Bilirubin as a cholestatic agent. IV. Effect of bilirubin and sulfobromophthalein (BSP) on biliary manganese excretion.

These experiments demonstrate that the adminstration of bilirubin does not significantly alter biliary manganese excretion in manganese-loaded animals. Sulfobromophthalein sodium (BSP), which has been shown to afford prophylaxis against manganese-bilirubin cholestasis, significantly increases the biliary excretion of manganese. These results are meaningful in that they indicate that the amount of manganese per se in the bile is not critical in this cholestasis, and suggest that intracanalicular reactions are probably not etiologically critical in this model. They point to the conclusion that the critical cholestatic events are occurring within the hepatocyte. The results also indicate that the biliary excretion of manganese is obligate, and to some extent independent of bile flow. The critical cholestatic events are presumably mediated through the biochemical effects of either a manganese-bilirubin complex or of manganese and bilirubin acting separately but synergistically.