Hepato-renal transport of phenolsulfonphthalein in analbuminemic rats: albumin is essential for hepatic compensatory elimination of a nephrophilic ligand in animals with renal dysfunction.
To investigate a possible function of plasma albumin in partitioning organic anions into bile and urine, phenolsulfonphthalein (PSP) was administered intravenously and its in vivo fate was studied in normal and analbuminemic mutant rats (NAR). No significant change in the rate of PSP disappearance was observed in bilaterally nephrectomized normal rats. However, biliary excretion of the injected dye increased remarkably in nephrectomized normal rats. Intravenously injected PSP disappeared very rapidly from the circulation of NAR. Thus, the plasma clearance and distribution volume of PSP were significantly larger in NAR than in normal rats. Bilateral nephrectomy also failed to decrease the plasma clearance and distribution volume of the dye in NAR. In striking contrast to the experiments in normal rats, bilateral nephrectomy did not increase the biliary secretion of PSP in NAR. When PSP bound to equimolar albumin was injected into bilaterally nephrectomized NAR, the biliary excretion of PSP increased significantly with concomitant decrease in both plasma clearance and distribution volume of the dye. These results indicate that, in cases of renal transport dysfunction, albumin plays a critical role in hepatic compensatory excretion of PSP, a nephrophilic organic anion, whose molecular weight (MW 354) is close to the threshold value for partitioning a ligand to the eliminatory routes in liver and kidney of a rodent.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008634:Mersalyl / Q000494:pharmacology; D009392:Nephrectomy; D010635:Phenolphthaleins / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012709:Serum Albumin / Q000172:deficiency* / Q000378:metabolism; D013045:Species Specificity
D010635:Phenolphthaleins; D012709:Serum Albumin; D008634:Mersalyl; D010637:Phenolsulfonphthalein