Role of ligandin as a binding protein and as an enzyme in the biliary excretion of sulfobromophthalein.

The effect of butylated hydroxyanisole (BHA; 600 mg/kg i.p. daily, for 10 days) and trans-stilbene oxide (TSO; 400 mg/kg i.p. daily, for 4 days) on the in vitro hepatic activity of glutathione transferases, the hepatic content of organic anion binding proteins and the plasma disappearance and biliary excretion of sulfobromophthalein (BSP), phenol-3,6-dibromsulphthalein disulfonate and [3H]ouabain was investigated in mice (BHA) and rats (TSO). Both BHA and TSO increased glutathione transferase activity toward BSP (360 and 200%), hepatic ligandin content (160 and 120%) and the biliary excretion of BSP (370 and 85%). BSP-glutathione excretion was enhanced, indicating that BSP conjugation was also stimulated in vivo. In contrast to BSP, biliary excretion of phenol-3,6-dibromsulphthalein disulfonate and organic anion which is not biotransformed but binds to ligandin, was unaltered or slightly increased (29%) after BHA or TSO treatment, respectively. TSO administration also did not affect the excretion of ouabain, a compound that neither binds to ligandin nor is biotransformed before excretion. Induction of ligandin failed to influence the initial disappearance of BSP, phenol-3,6-dibromsulphthalein disulfonate or ouabain from plasma, suggesting that induction had no marked effect on the hepatic uptake of these compounds. These studies suggest that ligandin plays a more important role in the biliary excretion of BSP due to its enzymatic rather than its binding properties.