Role of plasma albumin in renal elimination of a mercapturic acid

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Abstract
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). I.v. injected S-benzyl-N-acetylcysteine rapidly disappeared from the circulation both in NAR and normal animals. Its plasma clearance was significantly higher in NAR (45.7 ml/kg per min) than in normal rats (25.2 ml/kg per min). 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 .mu.M ligand concentration. The mercapturic acid bound to plasma albumin with an association constant of 2.24 .times. 105 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 per min) and an increase in the urinary secretion of this ligand in NAR, 30 min after injection of the mercapturic acid (10 .mu.mol/kg body wt), 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. Apparently, albumin is important for the renal accumulation and urinary elimination of the circulating mercapturic acid.