Dibromosulphophthalein: its pharmacokinetics and binding to hepatic cytosol proteins in rats with acute renal failure.
1. The pharmacokinetics, biliary excretion and binding of dibromosulphophthalein (DBSP) to plasma proteins and hepatic cytosol proteins have been studied in male rats with glycerol-induced acute renal failure (ARF). 2. The rate constants for hepatic uptake, efflux from liver to plasma and excretion into bile were all significantly decreased in rats with ARF. Furthermore, the plasma clearance of DBSP was also reduced. 3. The initial (0-10 min) and maximum biliary excretion rates of DBSP were both diminished in animals with ARF. The maximum excretion rate occurred between 5-10 min in control rats and 10-15 min in rats with ARF. However, there was no statistically significant change in the percentage dose recovered from bile after 30 min. 4. The plasma-protein binding of DBSP was decreased in rats with ARF and this change was due to a significant reduction in the association constant for the primary binding sites. 5. The binding of DBSP to ligandin (Y protein) was reduced by about 38% in rats with ARF but no change was noted in binding to Z protein. Reduced binding to ligandin was accompanied by decreased total liver glutathione S-transferase (GST) activity and a 36% reduction in the GST activity of ligandin. 6. The results support the contention that altered hepatic handling of cholephilic dyes in rats with ARF may be due to reduced binding to ligandin.
Silberstein
D J
DJ
Department of Pharmacology, University of Leeds.
Bowmer
C J
CJ
Yates
M S
MS
D058186:Acute Kidney Injury / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000032:analysis / Q000201:enzymology / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002855:Chromatography, Thin Layer; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013448:Sulfobromophthalein / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
D001798:Blood Proteins; D011506:Proteins; D013448:Sulfobromophthalein; C012479:dibromosulphthalein; D005982:Glutathione Transferase