Role of plasma albumin in renal elimination of a mercapturic acid. Analyses in normal and mutant analbuminemic rats.
Biosynthesis of N-acetylcysteine S-conjugates of xenobiotics (mercapturic acids) occurs via interorgan metabolism and the renal transtubular transport system plays an important role in elimination of the final metabolites from the organism. To assess the behavior of a mercapturic acid in the circulation, plasma clearance of radioactive S-benzyl-N-acetylcysteine and its interaction with plasma proteins were studied in normal and mutant analbuminemic rats (NAR). Intravenously injected S-benzyl-N-acetylcysteine rapidly disappeared from the circulation both in NAR and normal animals. However, its plasma clearance was significantly higher in NAR (45.7 ml kg-1 min-1) than in normal rats (25.2 ml kg-1 min-1). Ultrafiltration analysis revealed that 18.4% and 80.1% of the mercapturate bound to plasma protein(s) from NAR and normal rats, respectively, at 50 microM ligand concentration. The mercapturic acid bound to plasma albumin with an association constant of 2.24 X 10(5) M-1 and the number of binding sites was 1.18/mol albumin. The binding was competitively inhibited by probenecid and L-tryptophan. Concomitant administration of this mercapturic acid with equimolar amounts of albumin resulted in a marked decrease in the plasma clearance (26.2 ml kg-1 min-1) and an increase in the urinary secretion of this ligand in NAR. 30 min after injection of the mercapturic acid (10 mumol/kg body weight), 27.3% and 60.4% of the injected dose was recovered from urine and kidneys of NAR and normal rats respectively. About 41% of the dose was recovered in NAR urine when the ligand was injected bound to an equimolar amount of albumin. These results suggested that albumin is important for the renal accumulation and urinary elimination of the circulating mercapturic acid.
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011922:Rats, Mutant Strains; D012709:Serum Albumin / Q000172:deficiency / Q000378:metabolism*; D014018:Tissue Distribution
D001798:Blood Proteins; D012709:Serum Albumin; D000111:Acetylcysteine; C029319:S-benzyl-N-acetyl-L-cysteine