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

Z. Gregus, C. D. Klaassen

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 an 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.

Original languageEnglish
Pages (from-to)242-246
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume221
Issue number1
Publication statusPublished - 1982

Fingerprint

Sulfobromophthalein
Glutathione Transferase
Carrier Proteins
Butylated Hydroxyanisole
Enzymes
Ouabain
Phenol
Liver
Anions
Hepatobiliary Elimination
Glutathione

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of ligandin as a binding protein and as an enzyme in the biliary excretion of sulfobromophthalein. / Gregus, Z.; Klaassen, C. D.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 221, No. 1, 1982, p. 242-246.

Research output: Contribution to journalArticle

@article{839408b4df3347ab8f91d954c9d6876d,
title = "Role of ligandin as a binding protein and as an enzyme in the biliary excretion of sulfobromophthalein",
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 an 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.",
author = "Z. Gregus and Klaassen, {C. D.}",
year = "1982",
language = "English",
volume = "221",
pages = "242--246",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Role of ligandin as a binding protein and as an enzyme in the biliary excretion of sulfobromophthalein

AU - Gregus, Z.

AU - Klaassen, C. D.

PY - 1982

Y1 - 1982

N2 - 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 an 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.

AB - 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 an 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.

UR - http://www.scopus.com/inward/record.url?scp=0020081385&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020081385&partnerID=8YFLogxK

M3 - Article

C2 - 7062286

AN - SCOPUS:0020081385

VL - 221

SP - 242

EP - 246

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -