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

Z. Gregus,C. D. Klaassen

Published 1982 in Journal of Pharmacology and Experimental Therapeutics

ABSTRACT

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.

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