Transepithelial fate of bilirubin in the isolated rat kidney.
The renal handling of bilirubin in the rat was studied using an isolated kidney preparation by means of the determination of total pigment concentration decay in the perfusion medium and its renal clearance. Unconjugated bilirubin was incorporated in the perfusate at a concentration of about 4 microg/ml. In order to establish the potential role of secretion in renal handling of the pigment, experiments were also performed incorporating in the perfusate different doses of nicotinic acid (NA) (0.1 and 1.0 mM final concentration), which is considered an alternative substrate for the organic anion transport system, or probenecid (Prob) (0.1 and 1.0 mM final concentration), the classical inhibitor of organic anion transport process. The magnitude of pigment uptake from the perfusion medium, estimated by a first order exponential decay constant, was decreased in a dose-dependent way by NA (40 and 76% decrease for 0.1 and 1.0 mM of NA, respectively) and Prob (57 and 88% decrease for 0.1 and 1.0 mM of Prob, respectively). NA and Prob also induced a diminution in the ratio of pigment renal clearance to glomerular filtration rate (24 and 48% decrease for 0.1 and 1.0 mM of NA and 52 and 55% decrease for 0.1 and 1.0 mM of Prob). Based on these findings, it can be proposed that tubular secretion through the proximal cells contributes significantly to renal pigment depuration. In order to establish the possible contribution of cellular metabolism to the secretory process, a different set of experiments was conducted. The content of bilirubin mono and diconjugates (BMC and BDC) were determined in urine, in arterial and venous samples and in renal cortex. Studies performed using either an open or a closed circulating system, revealed that after conjugation in the renal cell, pigment derivatives can be secreted into both the tubule and the venous compartments. Total bilirubin concentration as well as the relative content of BMC and BDC in urine increased over time, representing the sum of both conjugates about 50% of the total pigment excreted by the end of experiments. Consequently, our results support the existence of a tubular transepithelial transport of bilirubin, playing the metabolism of the pigment an important role in this process.
Elías
M M
MM
Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR,Suipacha, Rosario, Argentina.
Mottino
A D
AD
Ochoa
E J
EJ
D000818:Animals; D019540:Area Under Curve; D001663:Bilirubin / Q000378:metabolism / Q000493:pharmacokinetics*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009525:Niacin / Q000494:pharmacology; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D009525:Niacin; D011339:Probenecid; D001663:Bilirubin