Reduced bile flow in rats during sulfobromophthalein infusion.

Male urethane-anesthetized Wistar rats with biliary fistulas were infused intravenously with sulfobromophthalein (BSP) or BSP-glutathione conjugate (BSP-GSH) (594 nmol/100 g/min) for 100 min. With BSP infusion the bile flow increased for 25 min and subsequently fell almost linearly. Biliary excretion of BSP-GSH correlated with the bile flow, whereas the hepatic concentration of this metabolite rose during infusion. The concentration of unconjugated BSP also increased in the liver. On the other hand, the infusion of BSP-GSH resulted in a long lasting choleresis accompanied by high biliary concentrations of BSP-GSH without a concurrent increase in the concentration of BSP-GSH in the liver. It is concluded that the increasing concentration of unconjugated BSP in the liver leads to an impaired excretion of BSP-GSH in the bile and concurrently to a reduction in bile flow. The conjugation with glutathione may be the rate-limiting step in the biliary excretion of BSP.